Skip to main content
Top
Published in: Radiation Oncology 1/2019

Open Access 01-12-2019 | Metastasis | Research

Increased heat shock protein 70 (Hsp70) serum levels and low NK cell counts after radiotherapy – potential markers for predicting breast cancer recurrence?

Authors: Anna Rothammer, Eva K. Sage, Caroline Werner, Stephanie E. Combs, Gabriele Multhoff

Published in: Radiation Oncology | Issue 1/2019

Login to get access

Abstract

Background

Breast cancer is the most common invasive tumor in women worldwide and the second cause of cancer-related deaths. After breast conserving surgery the tumor bed gets irradiated. Radiation-induced tumor cell death has been found to be associated with the release of damage-associated molecular patterns (DAMPs) including free Hsp70 that can stimulate inflammatory immune responses. Therefore, Hsp70 serum levels as well as the composition of lymphocyte subpopulations have been measured in breast cancer patients during therapy and in the follow-up period as potential predictors for clinical outcome.

Methods

The serum of 40 breast cancer patients, who received a breast-conserving surgery and adjuvant radiotherapy (RT) was examined for soluble, free Hsp70 using the R&D Human HSP70 DuoSet and lipHsp70 ELISA. Lymphocyte subpopulations and total lymphocyte counts were analysed by multiparameter flow cytometry in the peripheral blood. Blood samples were collected before (t1), after 30 Gy (t2) and 60 Gy (t3), 6 weeks (t4), 6 months (t5) and 1 year (t6) after RT. Clinical responses were assessed regularly up to 5 years after RT.

Results

Patients who developed a contralateral recurrence or metastases within the first 2 years after RT had significantly higher serum Hsp70 values at the end of RT (t3; p = 0.03) up to 6 weeks after RT (t4; p = 0.007) compared to patients who either remained disease-free or developed a secondary endometrial carcinoma. Clinicopathological parameters such as age, tumor size, grading and TNM-stage of the resected tumors, adjuvant chemotherapy and irradiation dose did not affect serum Hsp70 levels. Elevated free Hsp70 levels might be indicative for a chronic inflammatory response which could support tumor recurrence. Lymphocyte subpopulation analysis revealed lower NK cell counts after RT in recurrence/metastases patients as compared to disease-free patients. In contrast, no significant changes were observed in the proportion of T and B cells.

Conclusion

Longitudinal elevated serum levels of free Hsp70 up to 6 weeks after RT and dropping NK cell counts might be predictive for an unfavourable prognosis in patients with breast cancer.
Literature
1.
go back to reference Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez MC, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Malzer M, Uter W, Polgar C. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016;387:229–38.CrossRef Strnad V, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Gutierrez MC, Slampa P, Allgauer M, Lossl K, Polat B, Kovacs G, Fischedick AR, Wendt TG, Fietkau R, Hindemith M, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Potter R, Gall C, Malzer M, Uter W, Polgar C. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial. Lancet. 2016;387:229–38.CrossRef
2.
go back to reference Corradini S, Niyazi M, Niemoeller OM, Li M, Roeder F, Eckel R, Schubert-Fritschle G, Scheithauer HR, Harbeck N, Engel J, Belka C. Adjuvant radiotherapy after breast conserving surgery - a comparative effectiveness research study. Radiother Oncol. 2015;114:28–34.CrossRef Corradini S, Niyazi M, Niemoeller OM, Li M, Roeder F, Eckel R, Schubert-Fritschle G, Scheithauer HR, Harbeck N, Engel J, Belka C. Adjuvant radiotherapy after breast conserving surgery - a comparative effectiveness research study. Radiother Oncol. 2015;114:28–34.CrossRef
3.
go back to reference Speers C, Pierce LJ. Postoperative radiotherapy after breast-conserving surgery for early-stage breast Cancer: a review. JAMA Oncol. 2016;2:1075–82.CrossRef Speers C, Pierce LJ. Postoperative radiotherapy after breast-conserving surgery for early-stage breast Cancer: a review. JAMA Oncol. 2016;2:1075–82.CrossRef
4.
go back to reference Srikrishna G, Freeze HH. Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia. 2009;11:615–28.CrossRef Srikrishna G, Freeze HH. Endogenous damage-associated molecular pattern molecules at the crossroads of inflammation and cancer. Neoplasia. 2009;11:615–28.CrossRef
5.
go back to reference Huang J, Xie Y, Sun X, Zeh HJ III, Kang R, Lotze MT, Tang D. DAMPs, ageing, and cancer: the 'DAMP hypothesis. Ageing Res Rev. 2015;24:3–16.CrossRef Huang J, Xie Y, Sun X, Zeh HJ III, Kang R, Lotze MT, Tang D. DAMPs, ageing, and cancer: the 'DAMP hypothesis. Ageing Res Rev. 2015;24:3–16.CrossRef
6.
go back to reference Pandolfi F, Altamura S, Frosali S, Conti P. Key role of DAMP in inflammation, Cancer, and tissue repair. Clin Ther. 2016;38:1017–28.CrossRef Pandolfi F, Altamura S, Frosali S, Conti P. Key role of DAMP in inflammation, Cancer, and tissue repair. Clin Ther. 2016;38:1017–28.CrossRef
7.
go back to reference Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, Bracci L, Breckpot K, Brough D, Buque A, Castro MG, Cirone M, Colombo MI, Cremer I, Demaria S, Dini L, Eliopoulos AG, Faggioni A, Formenti SC, Fucikova J, Gabriele L, Gaipl US, Galon J, Garg A, Ghiringhelli F, Giese NA, Guo ZS, Hemminki A, Herrmann M, Hodge JW, Holdenrieder S, Honeychurch J, Hu HM, Huang X, Illidge TM, Kono K, Korbelik M, Krysko DV, Loi S, Lowenstein PR, Lugli E, Ma Y, Madeo F, Manfredi AA, Martins I, Mavilio D, Menger L, Merendino N, Michaud M, Mignot G, Mossman KL, Multhoff G, Oehler R, Palombo F, Panaretakis T, Pol J, Proietti E, Ricci JE, Riganti C, Rovere-Querini P, Rubartelli A, Sistigu A, Smyth MJ, Sonnemann J, Spisek R, Stagg J, Sukkurwala AQ, Tartour E, Thorburn A, Thorne SH, Vandenabeele P, Velotti F, Workenhe ST, Yang H, Zong WX, Zitvogel L, Kroemer G, Galluzzi L. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3:e955691.CrossRef Kepp O, Senovilla L, Vitale I, Vacchelli E, Adjemian S, Agostinis P, Apetoh L, Aranda F, Barnaba V, Bloy N, Bracci L, Breckpot K, Brough D, Buque A, Castro MG, Cirone M, Colombo MI, Cremer I, Demaria S, Dini L, Eliopoulos AG, Faggioni A, Formenti SC, Fucikova J, Gabriele L, Gaipl US, Galon J, Garg A, Ghiringhelli F, Giese NA, Guo ZS, Hemminki A, Herrmann M, Hodge JW, Holdenrieder S, Honeychurch J, Hu HM, Huang X, Illidge TM, Kono K, Korbelik M, Krysko DV, Loi S, Lowenstein PR, Lugli E, Ma Y, Madeo F, Manfredi AA, Martins I, Mavilio D, Menger L, Merendino N, Michaud M, Mignot G, Mossman KL, Multhoff G, Oehler R, Palombo F, Panaretakis T, Pol J, Proietti E, Ricci JE, Riganti C, Rovere-Querini P, Rubartelli A, Sistigu A, Smyth MJ, Sonnemann J, Spisek R, Stagg J, Sukkurwala AQ, Tartour E, Thorburn A, Thorne SH, Vandenabeele P, Velotti F, Workenhe ST, Yang H, Zong WX, Zitvogel L, Kroemer G, Galluzzi L. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology. 2014;3:e955691.CrossRef
8.
go back to reference Qin X, Ma D, Tan YX, Wang HY, Cai Z. The role of necroptosis in cancer: a double-edged sword? Biochim Biophys Acta Rev Cancer. 2019;1871:259–66.CrossRef Qin X, Ma D, Tan YX, Wang HY, Cai Z. The role of necroptosis in cancer: a double-edged sword? Biochim Biophys Acta Rev Cancer. 2019;1871:259–66.CrossRef
9.
go back to reference Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013;38(2):209–23.CrossRef Kaczmarek A, Vandenabeele P, Krysko DV. Necroptosis: the release of damage-associated molecular patterns and its physiological relevance. Immunity. 2013;38(2):209–23.CrossRef
10.
go back to reference Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene. 2016;35:5931–41.CrossRef Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene. 2016;35:5931–41.CrossRef
11.
go back to reference Rückert M, Deloch L, Fietkau R, Frey B, Hecht M, Gaipl US. Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies. Strahlenther Onkol. 2018;194:509–19.CrossRef Rückert M, Deloch L, Fietkau R, Frey B, Hecht M, Gaipl US. Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies. Strahlenther Onkol. 2018;194:509–19.CrossRef
12.
go back to reference Gunther S, Ostheimer C, Stangl S, Specht HM, Mozes P, Jesinghaus M, Vordermark D, Combs SE, Peltz F, Jung MP, Multhoff G. Correlation of Hsp70 serum levels with Gross tumor volume and composition of lymphocyte subpopulations in patients with squamous cell and adeno non-small cell lung Cancer. Front Immunol. 2015;6:556.CrossRef Gunther S, Ostheimer C, Stangl S, Specht HM, Mozes P, Jesinghaus M, Vordermark D, Combs SE, Peltz F, Jung MP, Multhoff G. Correlation of Hsp70 serum levels with Gross tumor volume and composition of lymphocyte subpopulations in patients with squamous cell and adeno non-small cell lung Cancer. Front Immunol. 2015;6:556.CrossRef
13.
go back to reference Ostheimer C, Gunther S, Bache M, Vordermark D, Multhoff G. Dynamics of heat shock protein 70 serum levels as a predictor of clinical response in non-small-cell lung Cancer and correlation with the hypoxia-related marker Osteopontin. Front Immunol. 2017;8:1305.CrossRef Ostheimer C, Gunther S, Bache M, Vordermark D, Multhoff G. Dynamics of heat shock protein 70 serum levels as a predictor of clinical response in non-small-cell lung Cancer and correlation with the hypoxia-related marker Osteopontin. Front Immunol. 2017;8:1305.CrossRef
14.
go back to reference Breuninger S, Erl J, Knape C, Gunther S, Regel I, Rödel F, Gaipl US, Thorsteinsdottier J, Giannitrapani L, Dickinson AM, Multhoff G. Quantitative analysis of liposomal heat shock proetein 70 (Hsp70) in the blood of tumor patients using a novel lipHsp70 ELISA. Clin Can Immunol. 2014;5:5. Breuninger S, Erl J, Knape C, Gunther S, Regel I, Rödel F, Gaipl US, Thorsteinsdottier J, Giannitrapani L, Dickinson AM, Multhoff G. Quantitative analysis of liposomal heat shock proetein 70 (Hsp70) in the blood of tumor patients using a novel lipHsp70 ELISA. Clin Can Immunol. 2014;5:5.
15.
go back to reference Gunaldi M, Afsar CU, Okuturlar Y, Gedikbasi A, Kocoglu H, Kural A, Akarsu C, Gunduz U, Tiken EE. Elevated serum levels of heat shock protein 70 are associated with breast cancer. Tohoku J Exp Med. 2015;236:97–102.CrossRef Gunaldi M, Afsar CU, Okuturlar Y, Gedikbasi A, Kocoglu H, Kural A, Akarsu C, Gunduz U, Tiken EE. Elevated serum levels of heat shock protein 70 are associated with breast cancer. Tohoku J Exp Med. 2015;236:97–102.CrossRef
16.
go back to reference Ren B, Luo S, Xu F, Zou G, Xu G, He J, Huang Y, Zhu H, Li Y. The expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in peripheral blood of patients with HCC and lung cancer. Cell Stress Chaperones. 2017;22:237–44.CrossRef Ren B, Luo S, Xu F, Zou G, Xu G, He J, Huang Y, Zhu H, Li Y. The expression of DAMP proteins HSP70 and cancer-testis antigen SPAG9 in peripheral blood of patients with HCC and lung cancer. Cell Stress Chaperones. 2017;22:237–44.CrossRef
17.
go back to reference Jubran R, Kocsis J, Garam N, Malati E, Gombos T, Barabas L, Graf L, Prohaszka Z, Fishelson Z. Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: risk indicators in colorectal cancer. Int J Cancer. 2017;141:2329–35.CrossRef Jubran R, Kocsis J, Garam N, Malati E, Gombos T, Barabas L, Graf L, Prohaszka Z, Fishelson Z. Circulating mitochondrial stress 70 protein/mortalin and cytosolic Hsp70 in blood: risk indicators in colorectal cancer. Int J Cancer. 2017;141:2329–35.CrossRef
18.
go back to reference Gunaldi M, Kocoglu H, Okuturlar Y, Gedikbasi A, Karabulut M, Alis H, Hursitoglu M. Heat shock protein 70 is a useful marker for predicting colorectal cancer. J BUON. 2015;20:1464–70.PubMed Gunaldi M, Kocoglu H, Okuturlar Y, Gedikbasi A, Karabulut M, Alis H, Hursitoglu M. Heat shock protein 70 is a useful marker for predicting colorectal cancer. J BUON. 2015;20:1464–70.PubMed
19.
go back to reference Radons J. The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones. 2016;21:379–404.CrossRef Radons J. The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones. 2016;21:379–404.CrossRef
20.
go back to reference Ciocca DR, Clark GM, Tandon AK, Fuqua SA, Welch WJ, McGuire WL. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst. 1993;85:570–4.CrossRef Ciocca DR, Clark GM, Tandon AK, Fuqua SA, Welch WJ, McGuire WL. Heat shock protein hsp70 in patients with axillary lymph node-negative breast cancer: prognostic implications. J Natl Cancer Inst. 1993;85:570–4.CrossRef
21.
go back to reference Dimas DT, Perlepe CD, Sergentanis TN, Misitzis I, Kontzoglou K, Patsouris E, Kouraklis G, Psaltopoulou T, Nonni A. The prognostic significance of Hsp70/Hsp90 expression in breast Cancer: a systematic review and meta-analysis. Anticancer Res. 2018;38:1551–62.PubMed Dimas DT, Perlepe CD, Sergentanis TN, Misitzis I, Kontzoglou K, Patsouris E, Kouraklis G, Psaltopoulou T, Nonni A. The prognostic significance of Hsp70/Hsp90 expression in breast Cancer: a systematic review and meta-analysis. Anticancer Res. 2018;38:1551–62.PubMed
22.
go back to reference Sage EK, Schmid TE, Sedelmayr M, Gehrmann M, Geinitz H, Duma MN, Combs SE, Multhoff G. Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. Radiother Oncol. 2016;118:176–80.CrossRef Sage EK, Schmid TE, Sedelmayr M, Gehrmann M, Geinitz H, Duma MN, Combs SE, Multhoff G. Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. Radiother Oncol. 2016;118:176–80.CrossRef
23.
go back to reference Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol. 2014;382:673–82.CrossRef Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol. 2014;382:673–82.CrossRef
24.
go back to reference Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014:149185.CrossRef Landskron G, De la Fuente M, Thuwajit P, Thuwajit C, Hermoso MA. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014;2014:149185.CrossRef
25.
go back to reference Wu Y, Antony S, Meitzler JL, Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett. 2014;345:164–73.CrossRef Wu Y, Antony S, Meitzler JL, Doroshow JH. Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett. 2014;345:164–73.CrossRef
26.
go back to reference Klee NS, McCarthy CG, Martinez-Quinones P, Webb RC. Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy. Ther Adv Cardiovasc Dis. 2017;11:297–317.CrossRef Klee NS, McCarthy CG, Martinez-Quinones P, Webb RC. Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy. Ther Adv Cardiovasc Dis. 2017;11:297–317.CrossRef
27.
go back to reference Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek AJ, Annaert W, Golab J, de WP, Vandenabeele P, Agostinis P. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 2012;31:1062–79.CrossRef Garg AD, Krysko DV, Verfaillie T, Kaczmarek A, Ferreira GB, Marysael T, Rubio N, Firczuk M, Mathieu C, Roebroek AJ, Annaert W, Golab J, de WP, Vandenabeele P, Agostinis P. A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death. EMBO J. 2012;31:1062–79.CrossRef
28.
go back to reference Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghiringhelli F, di VF, Zitvogel L, Kroemer G. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334:1573–7.CrossRef Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghiringhelli F, di VF, Zitvogel L, Kroemer G. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science. 2011;334:1573–7.CrossRef
29.
go back to reference Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Genin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, Andre F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med. 2009;15:1170–8.CrossRef Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, Vermaelen K, Panaretakis T, Mignot G, Ullrich E, Perfettini JL, Schlemmer F, Tasdemir E, Uhl M, Genin P, Civas A, Ryffel B, Kanellopoulos J, Tschopp J, Andre F, Lidereau R, McLaughlin NM, Haynes NM, Smyth MJ, Kroemer G, Zitvogel L. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med. 2009;15:1170–8.CrossRef
30.
go back to reference Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, Portela Catani JP, Hannani D, Duret H, Steegh K, Martins I, Schlemmer F, Michaud M, Kepp O, Sukkurwala AQ, Menger L, Vacchelli E, Droin N, Galluzzi L, Krzysiek R, Gordon S, Taylor PR, Van EP, Solary E, Smyth MJ, Zitvogel L, Kroemer G. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity. 2013;38:729–41.CrossRef Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, Portela Catani JP, Hannani D, Duret H, Steegh K, Martins I, Schlemmer F, Michaud M, Kepp O, Sukkurwala AQ, Menger L, Vacchelli E, Droin N, Galluzzi L, Krzysiek R, Gordon S, Taylor PR, Van EP, Solary E, Smyth MJ, Zitvogel L, Kroemer G. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity. 2013;38:729–41.CrossRef
31.
go back to reference Eike LM, Mauseth B, Camilio KA, Rekdal O, Sveinbjornsson B. The Cytolytic amphipathic beta(2,2)-amino acid LTX-401 induces DAMP release in melanoma cells and causes complete regression of B16 melanoma. PLoS One. 2016;11:e0148980.CrossRef Eike LM, Mauseth B, Camilio KA, Rekdal O, Sveinbjornsson B. The Cytolytic amphipathic beta(2,2)-amino acid LTX-401 induces DAMP release in melanoma cells and causes complete regression of B16 melanoma. PLoS One. 2016;11:e0148980.CrossRef
32.
go back to reference Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:282–6.CrossRef Elliott MR, Chekeni FB, Trampont PC, Lazarowski ER, Kadl A, Walk SF, Park D, Woodson RI, Ostankovich M, Sharma P, Lysiak JJ, Harden TK, Leitinger N, Ravichandran KS. Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature. 2009;461:282–6.CrossRef
33.
go back to reference Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005;65:5238–47.CrossRef Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005;65:5238–47.CrossRef
34.
go back to reference Stangl S, Tontcheva N, Sievert W, Shevtsov M, Niu M, Schmid TE, Pigorsch S, Combs SE, Haller B, Balermpas P, Rodel F, Rodel C, Fokas E, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Stuschke M, Grosu AL, Abdollahi A, Debus J, Belka C, Maihofer C, Monnich D, Zips D, Multhoff G. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: a multicentre retrospective study of the German Cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2018;142:1911–25.CrossRef Stangl S, Tontcheva N, Sievert W, Shevtsov M, Niu M, Schmid TE, Pigorsch S, Combs SE, Haller B, Balermpas P, Rodel F, Rodel C, Fokas E, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Stuschke M, Grosu AL, Abdollahi A, Debus J, Belka C, Maihofer C, Monnich D, Zips D, Multhoff G. Heat shock protein 70 and tumor-infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: a multicentre retrospective study of the German Cancer consortium radiation oncology group (DKTK-ROG). Int J Cancer. 2018;142:1911–25.CrossRef
35.
go back to reference Campian JL, Piotrowski AF, Ye X, Hakim FT, Rose J, Yan XY, Lu Y, Gress R, Grossman SA. Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide. J Neuro-Oncol. 2017;135:343–51.CrossRef Campian JL, Piotrowski AF, Ye X, Hakim FT, Rose J, Yan XY, Lu Y, Gress R, Grossman SA. Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide. J Neuro-Oncol. 2017;135:343–51.CrossRef
36.
go back to reference Gustafson MP, Bornschlegl S, Park SS, Gastineau DA, Roberts LR, Dietz AB, Hallemeier CL. Comprehensive assessment of circulating immune cell populations in response to stereotactic body radiation therapy in patients with liver cancer. Adv Radiat Oncol. 2017;2:540–7.CrossRef Gustafson MP, Bornschlegl S, Park SS, Gastineau DA, Roberts LR, Dietz AB, Hallemeier CL. Comprehensive assessment of circulating immune cell populations in response to stereotactic body radiation therapy in patients with liver cancer. Adv Radiat Oncol. 2017;2:540–7.CrossRef
37.
go back to reference Rühle PF, Goerig N, Wunderlich R, Fietkau R, Gaipl US, Strnad A, Frey B. Modulations in the peripheral immune system of glioblastoma patient is connected to therapy and tumor progression-a case report from the IMMO-GLIO-01 trial. Front Neurol. 2017;8:296.CrossRef Rühle PF, Goerig N, Wunderlich R, Fietkau R, Gaipl US, Strnad A, Frey B. Modulations in the peripheral immune system of glioblastoma patient is connected to therapy and tumor progression-a case report from the IMMO-GLIO-01 trial. Front Neurol. 2017;8:296.CrossRef
38.
go back to reference Multhoff G, Hightower LE. Cell surface expression of heat shock proteins and the immune response. Cell Stress Chaperones. 1996;1:167–76.CrossRef Multhoff G, Hightower LE. Cell surface expression of heat shock proteins and the immune response. Cell Stress Chaperones. 1996;1:167–76.CrossRef
39.
go back to reference Multhoff G, Mizzen L, Winchester CC, Milner CM, Wenk S, Eissner G, Kampinga HH, Laumbacher B, Johnson J. Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. Exp Hematol. 1999;27:1627–36.CrossRef Multhoff G, Mizzen L, Winchester CC, Milner CM, Wenk S, Eissner G, Kampinga HH, Laumbacher B, Johnson J. Heat shock protein 70 (Hsp70) stimulates proliferation and cytolytic activity of natural killer cells. Exp Hematol. 1999;27:1627–36.CrossRef
Metadata
Title
Increased heat shock protein 70 (Hsp70) serum levels and low NK cell counts after radiotherapy – potential markers for predicting breast cancer recurrence?
Authors
Anna Rothammer
Eva K. Sage
Caroline Werner
Stephanie E. Combs
Gabriele Multhoff
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2019
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/s13014-019-1286-0

Other articles of this Issue 1/2019

Radiation Oncology 1/2019 Go to the issue