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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2021

Open Access 01-12-2021 | Breast Cancer | Review

The immunomodulatory effects of endocrine therapy in breast cancer

Authors: Huanhuan Huang, Jun Zhou, Hailong Chen, Jiaxin Li, Chao Zhang, Xia Jiang, Chao Ni

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

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Abstract

Endocrine therapies with SERMs (selective estrogen receptor modulators) or SERDs (selective estrogen receptor downregulators) are standard therapies for patients with estrogen receptor (ER)-positive breast cancer. Multiple small molecule inhibitors targeting the PI3K-AKT-mTOR pathway or CDK4/6 have been developed to be used in combination with anti-estrogen drugs to overcome endocrine resistance. In addition to their direct antitumor effects, accumulating evidence has revealed the tumor immune microenvironment (TIM)-modulating effects of these therapeutic strategies, which have not been properly acknowledged previously. The immune microenvironment of breast tumors plays a crucial role in tumor development, metastasis and treatment response to endocrine therapy and immunotherapy. Therefore, in our current work, we comprehensively review the immunomodulatory effect of endocrine therapy and discuss its potential applications in combination with immune checkpoint inhibitors in breast cancer treatment.
Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.PubMedCrossRef
2.
3.
4.
Presti D, Quaquarini E. The PI3K/AKT/mTOR and CDK4/6 Pathways in Endocrine Resistant HR+/HER2- Metastatic Breast Cancer: Biological Mechanisms and New Treatments. Cancers (Basel). 2019;11(9):1242.CrossRef
5.
Beck JT, Hortobagyi GN, Campone M, Lebrun F, Deleu I. Rug HSo, et al. Everolimus plus exemestane as first-line therapy in HR+, HER2- advanced breast cancer in BOLERO-2. Breast Cancer Res Treat. 2014;43(3):459–67.CrossRef
6.
Fabrice A, Eva C, Gabor R, Mario C, Sibylle L. S RH, et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380(20):1929–40.CrossRef
7.
Jones RH, Casbard A, Carucci M, Cox C, Butler R, Alchami F, et al. Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2020;21(3):345–57.PubMedPubMedCentralCrossRef
8.
Turner NC, Slamon DJ, Ro J, Bondarenko I, Im SA, Masuda N, et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med. 2018;379(20):1926–36.PubMedCrossRef
9.
Im SA, Lu YS, Bardia A, Harbeck N, Colleoni M, Franke F, et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med. 2019;381(14):307–16.PubMedCrossRef
10.
Tower H, Ruppert M, Britt K. The Immune Microenvironment of Breast Cancer Progression. Cancers (Basel). 2019;11(9):1375.CrossRef
11.
Abrahamsson A, Rodriguez GV, Dabrosin C. Fulvestrant-mediated attenuation of the innate immune response decreases ER+ breast cancer growth in vivo more effectively than tamoxifen. Cancer Res. 2020:canres.1705.2020.
12.
Joffroy CM, Buck MB, Stope MB, Popp SL, Pfizenmaier K, Knabbe C. Antiestrogens Induce Transforming Growth Factor β–Mediated Immunosuppression in Breast Cancer. Cancer Res. 2010;70(4):1314–22.PubMedCrossRef
13.
Wang X, Simpson ER, Brown KA. Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer. J Steroid Biochem Mol Biol. 2015;153:35–44.PubMedCrossRef
14.
Purohit A, Newman SP, Reed MJ. The role of cytokines in regulating estrogen synthesis: implications for the etiology of breast cancer. Breast Cancer Res. 2002;4(2):65–9.PubMedPubMedCentralCrossRef
15.
Magnani L, Frige G, Gadaleta RM, Corleone G, Fabris S, Kempe H, et al. Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ERα metastatic breast cancer. Nat Genet. 2017;49(3):444–50.PubMedPubMedCentralCrossRef
16.
17.
Choi J, Gyamfi J, Jang H, Koo JS. The role of tumor-associated macrophage in breast cancer biology. Histol Histopathol. 2018;33(2):133–45.PubMed
18.
Segovia-Mendoza M, Morales-Montor J. Immune Tumor Microenvironment in Breast Cancer and the Participation of Estrogen and Its Receptors in Cancer Physiopathology. Front Immunol. 2019;10:348.PubMedPubMedCentralCrossRef
19.
Vegeto E, Ghisletti S, Meda C, Etteri S, Belcredito S, Maggi A. Regulation of the lipopolysaccharide signal transduction pathway by 17beta-estradiol in macrophage cells. J Steroid Biochem Mol Biol. 2004;91(1-2):59–66.PubMedCrossRef
20.
Kramer PR. S F Kramer, Guan G. 17 beta-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages. Arthritis Rheum. 2004;50(6):1967–75.PubMedCrossRef
21.
Rogers A, Eastell R. The effect of 17beta-estradiol on production of cytokines in cultures of peripheral blood. Bone. 2001;29(1):30–4.PubMedCrossRef
22.
Nilsson N, Carlsten H. Estrogen induces suppression of natural killer cell cytotoxicity and augmentation of polyclonal B cell activation. Cell Immunol. 1994;158(1):131–9.PubMedCrossRef
23.
Jiang X, Ellison S, Alarid E, Shapiro DJ. Interplay between the levels of estrogen and estrogen receptor controls the level of the granzyme inhibitor, proteinase inhibitor 9 and susceptibility to immune surveillance by natural killer cells. Oncogene. 2007;26(28):4106–14.PubMedCrossRef
24.
25.
Liu HY, Buenafe AC, Matejuk A, Ito A, Zamora A, Dwyer J, et al. Estrogen inhibition of EAE involves effects on dendritic cell function. J Neurosci Res. 2002;70:238–48.PubMedCrossRef
26.
Xiao BG, Liu X, Link H. Antigen-specific T cell functions are suppressed over the estrogen-dendritic cell-indoleamine 2, 3-dioxygenase axis. Steroids. 2004;69(10):653–9.PubMedCrossRef
27.
McMurray RW, Ndebele K, Hardy KJ, Jenkins JK. 17-β-estradiol suppresses IL-2 and IL-2 receptor. Cytokine. 2001;14(6):324–33.PubMedCrossRef
28.
Polanczyk MJ, Carson BD, Subramanian S, Afentoulis M, Vandenbark AA, Ziegler SF, et al. Cutting edge: estrogen drives expansion of the CD4+ CD25+ regulatory T cell compartment. J Immunol. 2004;173(4):2227–30.PubMedCrossRef
29.
Svoronos N, Perales-Puchalt A, Allegrezza MJ, Rutkowski MR, Payne KK, Tesone AJ, et al. Tumor cell–independent estrogen signaling drives disease progression through mobilization of myeloid-derived suppressor cells. Cancer Discov. 2017;7(1):72–85.PubMedCrossRef
30.
Polanczyk MJ, Hopke C, Vandenbark AA, Offner H. Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). Int Immunol. 2007;19(3):337–43.PubMedCrossRef
31.
Chung HH, Or YZ, Shrestha S, Loh JT, Lim CL, Ong Z, et al. Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution. Sci Rep. 2017;7:46485.PubMedPubMedCentralCrossRef
32.
Zhang W, Shen Y, Huang H, Pan S, Jiang J, Chen W, et al. A Rosetta Stone for Breast Cancer: Prognostic Value and Dynamic Regulation of Neutrophil in Tumor Microenvironment. Front Immunol. 2020;11:1779.PubMedPubMedCentralCrossRef
33.
Traboulsi T, Ezzy ME, Gleason JL, Mader S. Antiestrogens: structure-activity relationships and use in breast cancer treatment. J Mol Endocrinol. 2017;58(1):R15–31.PubMedCrossRef
34.
35.
Komi J, Lassila O. Antioestrogens enhance tumour necrosis factor receptor 2 (TNF-R2) expression and TNF-R2-mediated proliferation in activated T cells. Scand J Immunol. 1998;48(3):254–60.PubMedCrossRef
36.
Richards JO, Albers AJ, Smith TS, Tjoe JA. NK cell-mediated antibody-dependent cellular cytotoxicity is enhanced by tamoxifen in HER2/neu non-amplified, but not HER2/neu-amplified, breast cancer cells. Cancer Immunol Immunother. 2016;65(11):1325–35.PubMedCrossRef
37.
Nalbandian G, Paharkova-Vatchkova V, Mao A, Nale S, Kovats S. The selective estrogen receptor modulators, tamoxifen and raloxifene, impair dendritic cell differentiation and activation. J Immunol. 2005;175(4):2666–75.PubMedCrossRef
38.
Corriden R, Hollands A, Olson J, Derieux J, Lopez J, Chang JT, et al. Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide. Nat Commun. 2015;6(1):1–8.CrossRef
39.
Flores R, Döhrmann S, Schaal C, Hakkim A, Nizet V, Corriden R. The selective estrogen receptor modulator raloxifene inhibits neutrophil extracellular trap formation. Front Immunol. 2016;7:566.PubMedPubMedCentralCrossRef
40.
Márquez-Garbán DC, Deng G, Comin-Anduix B, Garcia AJ, Xing Y, Chen H-W, et al. Antiestrogens in combination with immune checkpoint inhibitors in breast cancer immunotherapy. J Steroid Biochem Mol Biol. 2019;193:105415.PubMedPubMedCentralCrossRef
41.
Chan MS, Wang L, Felizola SJ, Ueno T, Toi M, Loo W, et al. Changes of tumor infiltrating lymphocyte subtypes before and after neoadjuvant endocrine therapy in estrogen receptor-positive breast cancer patients–an immunohistochemical study of Cd8+ and FOXp3+ using double immunostaining with correlation to the pathobiological response of the patients. Int J Biol Markers. 2012;27(4):295–304.CrossRef
42.
Jingxuan W, Qingyuan Z, Shi J, Meiyan F, Xinmei K, Shu Z, et al. Immoderate inhibition of estrogen by anastrozole enhances the severity of experimental polyarthritis. Exp Gerontol. 2009;44(6-7):398–405.CrossRef
43.
Aggelakopoulou M, Kourepini E, Paschalidis I, Panoutsakopoulou V. ERβ in CD4+ T Cells Is Crucial for Ligand-Mediated Suppression of Central Nervous System Autoimmunity. J Immunol. 2016;196(12):4947–56.PubMedCrossRef
44.
Rao Q, Chen Y, Yeh C-R, Ding J, Li L, Chang C, et al. Recruited mast cells in the tumor microenvironment enhance bladder cancer metastasis via modulation of ERβ/CCL2/CCR2 EMT/MMP9 signals. Oncotarget. 2016;7(7):7842–55.PubMedCrossRef
45.
Sung N, García MDS, Dambaeva S, Beaman KD, Gilman-Sachs A, Kwak-Kim J. Gonadotropin-releasing hormone analogues lead to pro-inflammatory changes in T lymphocytes. Am J Reprod Immunol. 2016;76(1):50–8.PubMedCrossRef
46.
Xie S, Chen M, Yan B, He X, Chen X, Li D. Identification of a role for the PI3K/AKT/mTOR signaling pathway in innate immune cells. PLoS One. 2014;9(4):e94496.PubMedPubMedCentralCrossRef
47.
Abu-Eid R, Samara RN, Ozbun L, Abdalla MY, Berzofsky JA, Friedman KM, et al. Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway. Cancer Immunol Res. 2014;2(11):1080–9.PubMedPubMedCentralCrossRef
48.
Blanco B, Herrero-Sánchez C, Rodríguez-Serrano C, Sánchez-Barba M, del Cañizo MC. Comparative effect of two pan-class I PI3K inhibitors used as anticancer drugs on human T cell function. Int Immunopharmacol. 2015;28(1):675–85.PubMedCrossRef
49.
Sai J, Owens P, Novitskiy SV, Hawkins OE, Vilgelm AE, Yang J, et al. PI3K inhibition reduces mammary tumor growth and facilitates antitumor immunity and anti-PD1 responses. Clin Cancer Res. 2017;23(13):3371–84.PubMedCrossRef
50.
Choi J-H, Kim KH, Roh K-H, Jung H, Lee A, Lee J-Y, et al. A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice. Oncoimmunology. 2018;7(5):e1421890.PubMedPubMedCentralCrossRef
51.
Aragoneses-Fenoll L, Ojeda G, Montes-Casado M, Acosta-Ampudia Y, Dianzani U, Portolés P, et al. T-Cell-Specific Loss of the PI-3-Kinase p110α Catalytic Subunit Results in Enhanced Cytokine Production and Antitumor Response. Front Immunol. 2018;9:332.PubMedPubMedCentralCrossRef
52.
Teo ZL, Versaci S, Dushyanthen S, Caramia F, Savas P, Mintoff CP, et al. Combined CDK4/6 and PI3Kα inhibition is synergistic and immunogenic in triple-negative breast cancer. Cancer Res. 2017;77(22):6340–52.PubMedCrossRef
53.
Leverrier Y, Okkenhaug K, Sawyer C, Bilancio A, Vanhaesebroeck B, Ridley AJ. Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages. J Biol Chem. 2003;278(40):38437–42.PubMedCrossRef
54.
Houslay DM, Anderson KE, Chessa T, Kulkarni S, Fritsch R, Downward J, et al. Coincident signals from GPCRs and receptor tyrosine kinases are uniquely transduced by PI3Kβ in myeloid cells. Sci Signal. 2016;9(441):ra82.PubMedPubMedCentralCrossRef
55.
Schmid MC, Avraamides CJ, Dippold HC, Franco I, Foubert P, Ellies LG, et al. Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly Activate Myeloid Cell PI3Kg, A Single Convergent Point Promoting Tumor Inflammation and Progression. Cancer Cell. 2011;19(6):715–27.PubMedPubMedCentralCrossRef
56.
Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ, Gorjestani S, et al. PI3Kγ is a molecular switch that controls immune suppression. Nature. 2016;539(7629):437–42.PubMedPubMedCentralCrossRef
57.
De Henau O, Rausch M, Winkler D, Campesato LF, Liu C, Cymerman DH, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells. Nature. 2016;539(7629):443–7.PubMedPubMedCentralCrossRef
58.
Goulielmaki E, Bermudez-Brito M, Andreou M, Tzenaki N, Tzardi M, Ed B, et al. Pharmacological inactivation of the PI3K p110δ prevents breast tumour progression by targeting cancer cells and macrophages. Cell Death Dis. 2018;9(6):678.PubMedPubMedCentralCrossRef
59.
Ali K, Soond DR, Pineiro R, Hagemann T, Pearce W, Lim EL, et al. Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014;510(7505):407–11.PubMedPubMedCentralCrossRef
60.
Soond DR, Bjørgo E, Moltu K, Dale VQ, Patton DT, Torgersen KM, et al. PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood. 2010;115(11):2203–13.PubMedCrossRef
61.
Chiu H, Mallya S, Nguyen P, Mai A, Jackson LV, Winkler DG, et al. The Selective Phosphoinoside-3-Kinase p110δ Inhibitor IPI-3063 Potently Suppresses B Cell Survival, Proliferation, and Differentiation. Front Immunol. 2017;8:747.PubMedPubMedCentralCrossRef
62.
Gato-Cañas M. Morentin XMd, Blanco-Luquin I, Fernandez-Irigoyen J, Zudaire I, Liechtenstein T, et al. A core of kinase-regulated interactomes defines the neoplastic MDSC lineage. Oncotarget. 2015;6(29):27160–75.PubMedPubMedCentralCrossRef
63.
Arranz A, Doxaki C, Vergadi E, Torre YM, Vaporidi K, Lagoudaki ED, et al. Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization. Proc Natl Acad Sci U S A. 2012;109(24):9517–22.PubMedPubMedCentralCrossRef
64.
Nandagopal N, Ali AK, Komal AK, Lee S-H. The Critical Role of IL-15-PI3K-mTOR Pathway in Natural Killer Cell Effector Functions. Front Immunol. 2014;5:187.PubMedPubMedCentralCrossRef
65.
Marçais A, Cherfils-Vicini J, Viant C, Degouve S, Viel S, Fenis A, et al. The metabolic checkpoint kinase mTOR is essential for interleukin-15 signaling during NK cell development and activation. Nat Immunol. 2014;15(8):749–57.PubMedPubMedCentralCrossRef
66.
Haidinger M, Poglitsch M, Geyeregger R, Kasturi S, Zeyda M, Zlabinger GJ, et al. A versatile role of mammalian target of rapamycin in human dendritic cell function and differentiation. J Immunol. 2010;185(7):3919–31.PubMedCrossRef
67.
Zheng Y, Delgoffe GM, Meyer CF, Chan W, Powell JD. Anergic T cells are metabolically anergic. J Immunol. 2009;183(10):6095–101.PubMedCrossRef
68.
Pollizzi KN, Patel CH, Sun I-H, Oh M-H, Waickman AT, Wen J, et al. mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation. J Clin Invest. 2015;125(5):2090–108.PubMedPubMedCentralCrossRef
69.
Chaoul N, Fayolle C, Desrues B, Oberkampf M, Tang A, Ladant D, et al. Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication. Cancer Res. 2015;75(16):3279–91.PubMedCrossRef
70.
71.
Cao G, Wang Q, Li G, Meng Z, Liu H, Tong J, et al. mTOR inhibition potentiates cytotoxicity of Vγ4 γδ T cells via up-regulating NKG2D and TNF-α. J Leukoc Biol. 2016;100(5):1181–9.PubMedCrossRef
72.
Li H, Pauza CD. Rapamycin increases the yield and effector function of human γδ T cells stimulated in vitro. Cancer Immunol Immunother. 2011;60(3):361–70.PubMedCrossRef
73.
Procaccini C, Rosa VD, Galgani M, Abanni L, Calì G, Porcellini A, et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness. Immunity. 2010;33(6):929–41.PubMedPubMedCentralCrossRef
74.
Rosa VD, Galgani M, Porcellini A, Colamatteo A, Santopaolo M, Zuchegna C, et al. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants. Nat Immunol. 2015;16(11):1174–84.PubMedPubMedCentralCrossRef
75.
Deng J, Wang ES, Jenkins RW, Li S, Dries R, Yates K, et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 2018;8(2):216–33.PubMedCrossRef
76.
Schaer DA, Beckmann RP, Dempsey JA, Huber L, Forest A, Amaladas N, et al. The CDK4/6 inhibitor abemaciclib induces a T cell inflamed tumor microenvironment and enhances the efficacy of PD-L1 checkpoint blockade. Cell Rep. 2018;22(11):2978–94.PubMedCrossRef
77.
78.
Dabydeen SA, Kang K, Díaz-Cruz ES, Alamri A, Axelrod ML, Bouker KB, et al. Comparison of tamoxifen and letrozole response in mammary preneoplasia of ER and aromatase overexpressing mice defines an immune-associated gene signature linked to tamoxifen resistance. Carcinogenesis. 2015;36(1):122–32.PubMedCrossRef
79.
Jr BFB, Dehghani B, Foster S, Kurniawan A, Lopez FJ, Sherman LS. Treatment with selective estrogen receptor modulators regulates myelin specific T-cells and suppresses experimental autoimmune encephalomyelitis. Glia. 2009;57(7):777–90.CrossRef
80.
Li B, Li Y, Wang XY, Yan ZQ, Liu H, Liu GR, et al. Profile of differentially expressed intratumoral cytokines to predict the immune-polarizing side effects of tamoxifen in breast cancer treatment. Am J Cancer Res. 2015;5(2):726.PubMedPubMedCentral
81.
Huhn D, Martí-Rodrigo P, Mouron S, Hansel C, Tschapalda K, Haggblad M, et al. Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells. bioRxiv. 2019:715136.
82.
Rugo HS, Delord J-P, Im S-A, Ott PA, Piha-Paul SA, Bedard PL, et al. Safety and antitumor activity of pembrolizumab in patients with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer. Clin Cancer Res. 2018;24(12):2804–11.PubMedCrossRef
83.
Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedPubMedCentralCrossRef
84.
Jaini R, Loya MG, Eng C. Immunotherapeutic target expression on breast tumors can be amplified by hormone receptor antagonism: a novel strategy for enhancing efficacy of targeted immunotherapy. Oncotarget. 2017;8(20):32536.PubMedPubMedCentralCrossRef
85.
Komi J, Lassila O. Toremifene increases the expression of intercellular adhesion molecule-1 (ICAM-1) on MCF-7 breast cancer cells and Jurkat cells. Scand J Immunol. 2000;51(1):73–8.PubMedCrossRef
86.
Mor G, Kohen F, Garcia-Velasco J, Nilsen J, Brown W, Song J, et al. Regulation of fas ligand expression in breast cancer cells by estrogen: functional differences between estradiol and tamoxifen. J Steroid Biochem Mol Biol. 2000;73(5):185–94.PubMedCrossRef
87.
Svensson S, Abrahamsson A, Rodriguez GV, Olsson A-K, Jensen L, Cao Y, et al. CCL2 and CCL5 are novel therapeutic targets for estrogen-dependent breast cancer. Clin Cancer Res. 2015;21(16):3794–805.PubMedCrossRef
88.
Cuzick JSI, Cawthorn S. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015;16(1):67–75.PubMedPubMedCentralCrossRef
89.
Schild-Hay LJ, Leil TA, Divi RL, Olivero OA, Weston A, Poirier MC. Tamoxifen Induces Expression of Immune Response–Related Genes in Cultured Normal Human Mammary Epithelial Cells. Cancer Res. 2009;69(3):1150–5.PubMedPubMedCentralCrossRef
90.
Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science. 2018;361(6409):eaao4227.PubMedPubMedCentralCrossRef
91.
Simpson ER. Sources of estrogen and their importance. J Steroid Biochem Mol Biol. 2003;86(3-5):225–30.PubMedCrossRef
92.
De Placido S, Gallo C, De Laurentiis M, Bisagni G, Arpino G, Sarobba MG, et al. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial. Lancet Oncol. 2018;19(4):474–85.PubMedCrossRef
93.
94.
Braun DP, Crist KA, Shaheen F, Staren ED, Andrews S, Parker J. Aromatase inhibitors increase the sensitivity of human tumor cells to monocyte-mediated, antibody-dependent cellular cytotoxicity. Am J Surg. 2005;190(4):570–1.PubMedCrossRef
95.
Generali D, Bates G, Berruti A, Brizzi MP, Campo L, Bonardi S, et al. Immunomodulation of FOXP3+ regulatory T cells by the aromatase inhibitor letrozole in breast cancer patients. Clin Cancer Res. 2009;15(3):1046–51.PubMedCrossRef
96.
Guo D, Liu X, Zeng C, Cheng L, Song G, Hou X, et al. Estrogen receptor β activation ameliorates DSS-induced chronic colitis by inhibiting inflammation and promoting Treg differentiation. Int Immunopharmacol. 2019;77:105971.PubMedCrossRef
97.
Aponte-López A, Fuentes-Pananá EM, Cortes-Muñoz D, Muñoz-Cruz S. Mast Cell, the Neglected Member of the Tumor Microenvironment: Role in Breast Cancer. J Immunol Res. 2018;2018:2584243.PubMedPubMedCentralCrossRef
98.
Bense RD, Sotiriou C, Piccart-Gebhart MJ, Haanen JB, van Vugt MA, de Vries EG, et al. Relevance of tumor-infiltrating immune cell composition and functionality for disease outcome in breast cancer. J Natl Cancer Inst. 2016;109(1):djw192.PubMedCentralCrossRef
99.
Mello-Grand M, Singh V, Ghimenti C, Scatolini M, Regolo L, Grosso E, et al. Gene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer. Breast Cancer Res Treat. 2010;121(2):399–411.PubMedCrossRef
100.
Dunbier AK, Ghazoui Z, Anderson H, Salter J, Nerurkar A, Osin P, et al. Molecular profiling of aromatase inhibitor–treated postmenopausal breast tumors identifies immune-related correlates of resistance. Clin Cancer Res. 2013;19(10):2775–86.PubMedCrossRef
101.
Gao Q, Patani N, Dunbier AK, Ghazoui Z, Zvelebil M, Martin L-A, et al. Effect of aromatase inhibition on functional gene modules in estrogen receptor–positive breast cancer and their relationship with antiproliferative response. Clin Cancer Res. 2014;20(9):2485–94.PubMedCrossRef
102.
Liang X, Briaux A, Becette V, Benoist C, Boulai A, Chemlali W, et al. Molecular profiling of hormone receptor-positive, HER2-negative breast cancers from patients treated with neoadjuvant endocrine therapy in the CARMINA 02 trial (UCBG-0609). J Hematol Oncol. 2018;11(1):124.PubMedPubMedCentralCrossRef
103.
Skriver SK, Jensen M-B, Knoop AS, Ejlertsen B, Laenkholm A-V. Tumour-infiltrating lymphocytes and response to neoadjuvant letrozole in patients with early oestrogen receptor-positive breast cancer: analysis from a nationwide phase II DBCG trial. Breast Cancer Res. 2020;22(1):46.PubMedPubMedCentralCrossRef
104.
Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo W-L, Davies M, et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 2008;68(15):6084–91.PubMedPubMedCentralCrossRef
105.
Baselga J, Im S-A, Iwata H, Cortés J, Laurentiis MD, Jiang Z, et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;20(2):904–16.CrossRef
106.
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, et al. Pictilisib for oestrogen receptor-positive, aromatase inhibitorresistant, advanced or metastatic breast cancer (FERGI): A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2016;17(6):811–21.PubMedPubMedCentralCrossRef
107.
Juric D, Janku F, Rodón J, Burris HA, Mayer IA, Schuler M, et al. Alpelisib Plus Fulvestrant in PIK3CA-Altered and PIK3CA-Wild-Type Estrogen Receptor-Positive Advanced Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncol. 2019;5(2):e184475.PubMedCrossRef
108.
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, et al. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor-Positive Advanced Breast Cancer. Clin Cancer Res. 2018;24(18):4380–7.PubMedPubMedCentralCrossRef
109.
Kok K, Geering B, Vanhaesebroeck B. Regulation of phosphoinositide 3-kinase expression in health and disease. Trends Biochem Sci. 2009;34(3):115–27.PubMedCrossRef
110.
Blanco B, Herrero-Sánchez MC, Rodríguez-Serrano C, Sánchez-Barba M, Cañizo MCD. Profound blockade of T cell activation requires concomitant inhibition of different class I PI3K isoforms. Immunol Res. 2015;62(2):175–88.PubMedCrossRef
111.
Crane C, Panner A, Murray J, Wilson S, Xu H, Chen L, et al. PI (3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer. Oncogene. 2009;28(2):306–12.PubMedCrossRef
112.
Carvalho S, Milanezi F, Costa JL, Amendoeira I, Schmitt F. PIKing the right isoform: the emergent role of the p110β subunit in breast cancer. Virchows Archiv An Int J Pathol. 2010;456(3):235–43.CrossRef
113.
Crowder RJ, Phommaly C, Tao Y, Hoog J, Luo J, Perou CM, et al. PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor positive breast cancer. Cancer Res. 2009;69(9):3955–62.PubMedPubMedCentralCrossRef
114.
Hosford SR, Dillon LM, Bouley SJ, Rosati R, Yang W, Chen VS, et al. Combined Inhibition of Both p110α and p110β Isoforms of Phosphatidylinositol 3-Kinase Is Required for Sustained Therapeutic Effect in PTEN-Deficient, ER+ Breast Cancer. Clin Cancer Res. 2017;23(11):2795–805.PubMedCrossRef
115.
Araki K, Miyoshi Y. Mechanism of resistance to endocrine therapy in breast cancer: the important role of PI3K/Akt/mTOR in estrogen receptor-positive, HER2-negative breast cancer. Breast Cancer. 2018;25(4):392–401.PubMedCrossRef
116.
Zhang B, Ma Y, Guo H, Sun B, Niu R, Ying G, et al. Akt2 is required for macrophage chemotaxis. Eur J Immunol. 2009;39(3):894–901.PubMedCrossRef
117.
Wang J, Wan W, Sun R, Liu Y, Sun X, Ma D, et al. Reduction of Akt2 expression inhibits chemotaxis signal transduction in human breast cancer cells. Cell Signal. 2008;20(6):1025–34.PubMedCrossRef
118.
O'Shaughnessy J, Beck JT, Royce M. Everolimus-based combination therapies for HR+, HER2− metastatic breast cancer. Cancer Treat Rev. 2018;69:204–14.PubMedCrossRef
119.
Zeng H. mTOR signaling in immune cells and its implications for cancer immunotherapy. Cancer Lett. 2017;408:182–9.PubMedCrossRef
120.
Powell JD, Lerner CG, Schwartz RH. Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. J Immunol. 1999;162(5):2775–84.PubMedCrossRef
121.
Mercalli A, Calavita I, Dugnani E, Citro A, Cantarelli E, Nano R, et al. Rapamycin unbalances the polarization of human macrophages to M1. Immunology. 2013;140(2):179–90.PubMedPubMedCentralCrossRef
122.
Chen W, Ma T, Shen X-n, Xia X-f, Xu G-d, Bai X-l, et al. Macrophage-induced tumor angiogenesis is regulated by the TSC2-mTOR pathway. Cancer Res. 2012;72(6):1363–72.PubMedCrossRef
123.
Deng Y, Yang J, Luo F, Qian J, Liu R, Zhang D, et al. mTOR-mediated glycolysis contributes to the enhanced suppressive function of murine tumor-infiltrating monocytic myeloid-derived suppressor cells. Cancer Immunol Immunother. 2018;67(9):1355–64.PubMedCrossRef
124.
Wu T, Zhao Y, Wang H, Shao L, Wang R, Lu J, et al. mTOR masters monocytic myeloid-derived suppressor cells in mice with allografts or tumors. Sci Rep. 2016;6:20250.PubMedPubMedCentralCrossRef
125.
Amiel E, Everts B, Freitas TC, King IL, Curtis JD, Pearce EL, et al. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J Immunol. 2012;189(5):2151–8.PubMedCrossRef
126.
Ni C, Fang Q-Q, Chen W-Z, Jiang J-X, Jiang Z, Ye J, et al. Breast cancer-derived exosomes transmit lncRNA SNHG16 to induce CD73+γδ1 Treg cells. Signal Transduct Target Ther. 2020;5(1):41.PubMedPubMedCentralCrossRef
127.
Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im S-A, Masuda N, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial17. Lancet Oncol. 2016;17(4):425–39.PubMedCrossRef
128.
Tripathy D, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904–15.PubMedCrossRef
129.
Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol. 2019;6(1):116–24.PubMedCentralCrossRef
130.
Watanabe S, Kawamoto S, Ohtani N, Hara E. Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases. Cancer Sci. 2017;108(4):563–9.PubMedPubMedCentralCrossRef
131.
132.
Martinez GJ, Pereira RM, Äijö T, Kim EY, Marangoni F, Pipkin ME, et al. The transcription factor NFAT promotes exhaustion of activated CD8+ T cells. Immunity. 2015;42(2):265–78.PubMedPubMedCentralCrossRef
133.
Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810–21.CrossRefPubMed
134.
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. IMpassion130: updated overall survival (OS) from a global, randomized, double-blind, placebo-controlled, Phase III study of atezolizumab (atezo)+ nab-paclitaxel (nP) in previously untreated locally advanced or metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2019;37(15):suppl.
135.
Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, et al. Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance. Nature. 2018;553(7686):91–5.PubMedCrossRef
136.
Hu ZY, Xie N, Tian C, Yang X, Liu L, Li J, et al. Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance. EBioMedicine. 2018;32:111–8.PubMedPubMedCentralCrossRef
137.
Waks AG, Stover DG, Guerriero JL, Dillon D, Barry WT, Gjini E, et al. The Immune Microenvironment in Hormone Receptor-Positive Breast Cancer Before and After Preoperative Chemotherapy. Clin Cancer Res. 2019;25(15):4644–55.PubMedCrossRef
Metadata
Title
The immunomodulatory effects of endocrine therapy in breast cancer
Authors
Huanhuan Huang
Jun Zhou
Hailong Chen
Jiaxin Li
Chao Zhang
Xia Jiang
Chao Ni
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-020-01788-4

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