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BMC Cancer
Published in: BMC Cancer 1/2024

Open Access 01-12-2024 | Cytokines | Research

Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11

Authors: Christian Idel, Jonas Fleckner, Kirstin Plötze-Martin, Lotte Werner, Dirk Rades, Marie-Nicole Theodoraki, Linda Hofmann, Diana Huber, Anke Leichtle, Thomas K. Hoffmann, Karl-Ludwig Bruchhage, Ralph Pries

Published in: BMC Cancer | Issue 1/2024

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Abstract

Background

Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood.

Methods

Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements.

Results

Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11).

Conclusions

Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.
Literature
1.
Pfister DG, Spencer S, Adelstein D, Adkins D, Anzai Y, Brizel DM, et al. Head and neck cancers, version 2.2020, NCCN Clinical Practice guidelines in Oncology. J Natl Compr Cancer Netw. 2020;18(7):873–98.CrossRef
2.
Zhang P, Li S, Zhang T, Cui F, Shi JH, Zhao F, et al. Characterization of molecular subtypes in head and neck squamous cell carcinoma with distinct prognosis and treatment responsiveness. Front Cell Dev Biology. 2021;9:711348.CrossRef
3.
4.
Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiotherapy Oncology: J Eur Soc Therapeutic Radiol Oncol. 2021;156:281–93.CrossRef
5.
6.
7.
Ichiki Y, Taira A, Chikaishi Y, Matsumiya H, Mori M, Kanayama M, et al. Prognostic factors of advanced or postoperative recurrent non-small cell lung cancer targeted with immune check point inhibitors. J Thorac Disease. 2019;11(4):1117–23.CrossRef
8.
Ruckert M, Flohr AS, Hecht M, Gaipl US. Radiotherapy and the immune system: more than just immune suppression. Stem Cells. 2021;39(9):1155–65.PubMedCrossRef
9.
Bauer M, Goldstein M, Christmann M, Becker H, Heylmann D, Kaina B. Human monocytes are severely impaired in base and DNA double-strand break repair that renders them vulnerable to oxidative stress. Proc Natl Acad Sci USA. 2011;108(52):21105–10.PubMedPubMedCentralCrossRef
10.
Wunderlich R, Ernst A, Rodel F, Fietkau R, Ott O, Lauber K, et al. Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine milieu, but do not impact upon viability and phagocytic function. Clin Exp Immunol. 2015;179(1):50–61.PubMedCrossRef
11.
Hart L, Ogbonnaya A, Boykin K, Deyoung K, Bailey R, Heritage T, et al. Burden of chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer: a retrospective study from community oncology practices. Cancer Med. 2023;12(8):10020–30.PubMedPubMedCentralCrossRef
12.
Brandmaier A, Formenti SC. The impact of radiation therapy on innate and adaptive tumor immunity. Semin Radiat Oncol. 2020;30(2):139–44.PubMedCrossRef
13.
Li B, Ren M, Zhou X, Han Q, Cheng L. Targeting tumor-associated macrophages in head and neck squamous cell carcinoma. Oral Oncol. 2020;106: 104723.PubMedCrossRef
14.
Wagner F, Holig U, Wilczkowski F, Plesca I, Sommer U, Wehner R, et al. Neoadjuvant radiochemotherapy significantly alters the phenotype of plasmacytoid dendritic cells and 6-Sulfo LacNAc(+) monocytes in rectal cancer. Front Immunol. 2019;10:602.PubMedPubMedCentralCrossRef
15.
Tojo M, Horie H, Koinuma K, Miyato H, Tsukui H, Kaneko Y, et al. Programmed cell death ligand 1 expression on monocytes is inversely correlated with tumour response to preoperative chemoradiotherapy for locally advanced rectal cancer. Colorectal Dis. 2022;24(10):1140–9.CrossRef
16.
Stefater JA 3, Ren S, Lang RA, Duffield JS. Metchnikoff’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med. 2011;17(12):743–52.PubMedPubMedCentralCrossRef
17.
Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53(1–3):41–57.PubMedCrossRef
18.
19.
Patel AA, Zhang Y, Fullerton JN, Boelen L, Rongvaux A, Maini AA, et al. The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J Exp Med. 2017;214(7):1913–23.PubMedPubMedCentralCrossRef
20.
Boyette LB, Macedo C, Hadi K, Elinoff BD, Walters JT, Ramaswami B, et al. Phenotype, function, and differentiation potential of human monocyte subsets. PLoS ONE. 2017;12(4): e0176460.PubMedPubMedCentralCrossRef
21.
Idel C, Loyal K, Rades D, Hakim SG, Schumacher U, Bruchhage KL, et al. Smoking-, alcohol-, and age-related alterations of blood monocyte subsets and circulating CD4/CD8 T cells in head and neck cancer. Biology. 2022;11(5):658.PubMedPubMedCentralCrossRef
22.
Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, et al. Differential chemokine receptor expression and function in human monocyte subpopulations. J Leukoc Biol. 2000;67(5):699–704.PubMedCrossRef
23.
Polasky C, Steffen A, Loyal K, Lange C, Bruchhage KL, Pries R. Redistribution of monocyte subsets in obstructive sleep apnea syndrome patients leads to an imbalanced PD-1/PD-L1 cross-talk with CD4/CD8 T cells. J Immunol. 2021;206(1):51–8.PubMedCrossRef
24.
Kumaravel S, Singh S, Roy S, Venkatasamy L, White TK, Sinha S, et al. CXCL11-CXCR3 axis mediates tumor lymphatic cross talk and inflammation-induced tumor, promoting pathways in head and neck cancers. Am J Pathol. 2020;190(4):900–15.PubMedPubMedCentralCrossRef
25.
Wang X, Zhang J, Zhou G. The CXCL11-CXCR3A axis influences the infiltration of CD274 and IDO1 in oral squamous cell carcinoma. J oral Pathol Medicine: Official Publication Int Association Oral Pathologists Am Acad Oral Pathol. 2021;50(4):362–70.CrossRef
26.
Atun R, Jaffray DA, Barton MB, Bray F, Baumann M, Vikram B, et al. Expanding global access to radiotherapy. Lancet Oncol. 2015;16(10):1153–86.PubMedCrossRef
27.
28.
29.
Moriyama Y, Horita N, Kudo M, Shinkai M, Fujita H, Yamanaka T, et al. Monocyte nadir is a possible indicator for neutrophil nadir during lung cancer chemotherapy. Clin Respir J. 2017;11(4):453–8.PubMedCrossRef
30.
Ouyang W, Liu Y, Deng D, Zhou F, Xie C. The change in peripheral blood monocyte count: a predictor to make the management of chemotherapy-induced neutropenia. J Cancer Res Ther. 2018;14(Supplement):S565-570.PubMed
31.
Soeda A, Morita-Hoshi Y, Makiyama H, Morizane C, Ueno H, Ikeda M, et al. Regular dose of gemcitabine induces an increase in CD14 + monocytes and CD11c + dendritic cells in patients with advanced pancreatic cancer. Jpn J Clin Oncol. 2009;39(12):797–806.PubMedCrossRef
32.
Valdes-Ferrada J, Munoz-Durango N, Perez-Sepulveda A, Muniz S, Coronado-Arrazola I, Acevedo F, et al. Peripheral blood classical monocytes and plasma interleukin 10 are Associated to neoadjuvant chemotherapy response in breast cancer patients. Front Immunol. 2020;11: 1413.PubMedPubMedCentralCrossRef
33.
Cassetta L, Fragkogianni S, Sims AH, Swierczak A, Forrester LM, Zhang H, et al. Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell. 2019;35(4):588-e60210.PubMedPubMedCentralCrossRef
34.
35.
Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, et al. IL-17-producing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015;522(7556):345–8.PubMedPubMedCentralCrossRef
36.
Galluzzi L, Humeau J, Buque A, Zitvogel L, Kroemer G. Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Reviews Clin Oncol. 2020;17(12):725–41.CrossRef
37.
Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity. 2013;39(1):74–88.PubMedCrossRef
38.
39.
Ingalls RR, Golenbock DT. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J Exp Med. 1995;181(4):1473–9.PubMedCrossRef
40.
Postigo AA, Corbi AL, Sanchez-Madrid F, de Landazuri MO. Regulated expression and function of CD11c/CD18 integrin on human B lymphocytes. Relation between attachment to fibrinogen and triggering of proliferation through CD11c/CD18. J Exp Med. 1991;174(6):1313–22.PubMedCrossRef
41.
Dupuy AG, Caron E. Integrin-dependent phagocytosis - spreading from microadhesion to new concepts. J Cell Sci. 2008;121(11):1773–83.PubMedCrossRef
42.
McDermott DH, Halcox JPJ, Schenke WH, Waclawiw MA, Merrell MN, Epstein N, et al. Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis. Circ Res. 2001;89(5):401–7.PubMedCrossRef
43.
Tacke F, Alvarez D, Kaplan TJ, Jakubzick C, Spanbroek R, Llodra J, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007;117(1):185–94.PubMedPubMedCentralCrossRef
44.
Auffray C, Fogg D, Garfa M, Elain G, Join-Lambert O, Kayal S, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science. 2007;317(5838):666–70.PubMedCrossRef
45.
Jenei V, Burai S, Molnar T, Kardos B, Macsik R, Toth M, et al. Comparison of the immunomodulatory potential of platinum-based anti-cancer drugs and anthracyclins on human monocyte-derived cells. Cancer Chemother Pharmacol. 2023;91(1):53–66.PubMedCrossRef
46.
Kalbasi A, Komar C, Tooker GM, Liu M, Lee JW, Gladney WL, et al. Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma. Clin Cancer Res. 2017;23(1):137–48.CrossRef
47.
Mondini M, Loyher PL, Hamon P, Gerbe de Thore M, Laviron M, Berthelot K, et al. CCR2-dependent recruitment of tregs and monocytes following radiotherapy is associated with TNFalpha-mediated resistance. Cancer Immunol Res. 2019;7(3):376–87.PubMedCrossRef
48.
Shin SC, Lee KM, Kang YM, Kim K, Kim CS, Yang KH, et al. Alteration of cytokine profiles in mice exposed to chronic low-dose ionizing radiation. Biochem Biophys Res Commun. 2010;397(4):644–9.PubMedCrossRef
49.
Ye X, Liu J, Quan R, Lu Y, Zhang J. DKK1 affects survival of patients with head and neck squamous cell carcinoma by inducing resistance to radiotherapy and immunotherapy. Radiotherapy Oncology: J Eur Soc Therapeutic Radiol Oncol. 2023;181:109485.CrossRef
50.
Plattel WJ, Alsada ZN, van Imhoff GW, Diepstra A, van den Berg A, Visser L. Biomarkers for evaluation of treatment response in classical Hodgkin lymphoma: comparison of sGalectin-1, sCD163 and sCD30 with TARC. Br J Haematol. 2016;175(5):868–75.PubMedCrossRef
51.
Aderhold C, Umbreit C, Faber A, Sauter A, Sommer JU, Birk R, et al. Chemotherapeutic alteration of VEGF, PDGF and PDGFRalpha/beta expression under 5-FU vs. docetaxel in HPV-transformed squamous cell carcinoma compared to HPV-negative HNSCC in vitro. Anticancer Res. 2013;33(5):1951–61.PubMed
52.
Lin LH, Lin JS, Yang CC, Cheng HW, Chang KW, Liu CJ. Overexpression of platelet-derived growth factor and its receptor are correlated with oral tumorigenesis and poor prognosis in oral squamous cell carcinoma. Int J Mol Sci. 2020;21(7):2360.PubMedPubMedCentralCrossRef
53.
Graves DT, Grotendorst GR, Antoniades HN, Schwartz CJ, Valente AJ. Platelet-derived growth factor is not chemotactic for human peripheral blood monocytes. Exp Cell Res. 1989;180(2):497–503.PubMedCrossRef
54.
Gao YJ, Liu L, Li S, Yuan GF, Li L, Zhu HY, et al. Down-regulation of CXCL11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition. OncoTargets Therapy. 2018;11:7333–43.PubMedPubMedCentralCrossRef
55.
Hwang HJ, Lee YR, Kang D, Lee HC, Seo HR, Ryu JK, et al. Endothelial cells under therapy-induced senescence secrete CXCL11, which increases aggressiveness of breast cancer cells. Cancer Lett. 2020;490:100–10.PubMedCrossRef
56.
Wang G, Zhang Z, Zhong K, Wang Z, Yang N, Tang X, et al. CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma. Mol Therapy. 2023;31(1):134–53.CrossRef
57.
58.
Radmanic L, Simicic P, Bodulic K, Vince A, Zidovec-Lepej S. Antiviral treatment significantly reduces the levels of CXCL9, CXCL10 and CXCL11 in chronic hepatitis C. Cytokine. 2024;176:156529.PubMedCrossRef
59.
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.PubMedPubMedCentralCrossRef
60.
Probst HC, McCoy K, Okazaki T, Honjo T, van den Broek M. Resting dendritic cells induce peripheral CD8 + T cell tolerance through PD-1 and CTLA-4. Nat Immunol. 2005;6(3):280–6.PubMedCrossRef
61.
Keir ME, Liang SC, Guleria I, Latchman YE, Qipo A, Albacker LA, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med. 2006;203(4):883–95.PubMedPubMedCentralCrossRef
62.
Tsushima F, Yao S, Shin T, Flies A, Flies S, Xu H, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood. 2007;110(1):180–5.PubMedPubMedCentralCrossRef
63.
Dave K, Ali A, Magalhaes M. Increased expression of PD-1 and PD-L1 in oral lesions progressing to oral squamous cell carcinoma: a pilot study. Sci Rep. 2020;10(1):9705.PubMedPubMedCentralCrossRef
64.
Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11(11):3887–95.PubMedPubMedCentralCrossRef
65.
Sharpe AH, Pauken KE. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 2018;18(3):153–67.PubMedCrossRef
66.
Thibult ML, Mamessier E, Gertner-Dardenne J, Pastor S, Just-Landi S, Xerri L, et al. PD-1 is a novel regulator of human B-cell activation. Int Immunol. 2013;25(2):129–37.PubMedCrossRef
67.
Kuang DM, Peng C, Zhao Q, Wu Y, Chen MS, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology. 2010;51(1):154–64.PubMedCrossRef
68.
Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, van der Velden J, Kenter GG, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Mod Pathol. 2016;29(7):753–63.CrossRef
69.
Kim HR, Ha SJ, Hong MH, Heo SJ, Koh YW, Choi EC, et al. PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. Sci Rep. 2016;6: 36956.PubMedPubMedCentralCrossRef
70.
Shinchi Y, Ishizuka S, Komohara Y, Matsubara E, Mito R, Pan C, et al. The expression of PD-1 ligand 1 on macrophages and its clinical impacts and mechanisms in lung adenocarcinoma. Cancer Immunol Immunotherapy: CII. 2022;71(11):2645–61.PubMedCrossRef
71.
Kzhyshkowska J, Gudima A, Moganti K, Gratchev A, Orekhov A. Perspectives for monocyte/macrophage-based diagnostics of chronic inflammation. Transfus Med Hemother. 2016;43(2):66–77.CrossRef
72.
Wang NH, Lei Z, Yang HN, Tang Z, Yang MQ, Wang Y, et al. Radiation-induced PD-L1 expression in tumor and its microenvironment facilitates cancer-immune escape: a narrative review. Annals Translational Med. 2022;10(24):1406.CrossRef
Metadata
Title
Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11
Authors
Christian Idel
Jonas Fleckner
Kirstin Plötze-Martin
Lotte Werner
Dirk Rades
Marie-Nicole Theodoraki
Linda Hofmann
Diana Huber
Anke Leichtle
Thomas K. Hoffmann
Karl-Ludwig Bruchhage
Ralph Pries
Publication date
01-12-2024
Publisher
BioMed Central
Keyword
Cytokines
Published in
BMC Cancer / Issue 1/2024
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-024-12177-x

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