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Erschienen in: Strahlentherapie und Onkologie 8/2017

12.05.2017 | Original Article

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients

verfasst von: Eva K. Sage, Thomas E. Schmid, Hans Geinitz, Mathias Gehrmann, Michael Sedelmayr, Marciana N. Duma, Stephanie E. Combs, Gabriele Multhoff

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 8/2017

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Abstract

Background

Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects.

Patients and methods

A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period.

Results

Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3+ T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT.

Conclusion

Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells.
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Literatur
2.
3.
Zurück zum Zitat Pinkawa M, Piroth MD, Holy R, Djukic V, Klotz J, Krenkel B, Eble MJ (2011) Combination of dose escalation with technological advances (intensity-modulated and image-guided radiotherapy) is not associated with increased morbidity for patients with prostate cancer. Strahlenther Onkol 187(8):479–484. doi:10.1007/s00066-011-2249-z CrossRefPubMed Pinkawa M, Piroth MD, Holy R, Djukic V, Klotz J, Krenkel B, Eble MJ (2011) Combination of dose escalation with technological advances (intensity-modulated and image-guided radiotherapy) is not associated with increased morbidity for patients with prostate cancer. Strahlenther Onkol 187(8):479–484. doi:10.​1007/​s00066-011-2249-z CrossRefPubMed
6.
Zurück zum Zitat Pinkawa M (2015) Recent advances in definitive radiotherapy for prostate cancer. Eur Med J Oncol 3(1):41–48 Pinkawa M (2015) Recent advances in definitive radiotherapy for prostate cancer. Eur Med J Oncol 3(1):41–48
7.
Zurück zum Zitat Budach W, Sachkerer I (2014) Dose escalation: an update on randomised clinical trials. In: Geinitz R III (ed) Radiotherapy in prostate cancer. Medical radiology. Springer, Berlin, pp 89–93 Budach W, Sachkerer I (2014) Dose escalation: an update on randomised clinical trials. In: Geinitz R III (ed) Radiotherapy in prostate cancer. Medical radiology. Springer, Berlin, pp 89–93
8.
9.
Zurück zum Zitat Freedland SJ, Sutter ME, Dorey F, Aronson WJ (2003) Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology 61(2):365–369CrossRefPubMed Freedland SJ, Sutter ME, Dorey F, Aronson WJ (2003) Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology 61(2):365–369CrossRefPubMed
10.
Zurück zum Zitat Geinitz H, Riegel MG, Thamm R, Astner ST, Lewerenz C, Zimmermann F, Molls M, Nieder C (2012) Outcome after conformal salvage radiotherapy in patients with rising prostate-specific antigen levels after radical prostatectomy. Int J Radiat Oncol Biol Phys 82(5):1930–1937. doi:10.1016/j.ijrobp.2011.03.003 CrossRefPubMed Geinitz H, Riegel MG, Thamm R, Astner ST, Lewerenz C, Zimmermann F, Molls M, Nieder C (2012) Outcome after conformal salvage radiotherapy in patients with rising prostate-specific antigen levels after radical prostatectomy. Int J Radiat Oncol Biol Phys 82(5):1930–1937. doi:10.​1016/​j.​ijrobp.​2011.​03.​003 CrossRefPubMed
14.
Zurück zum Zitat Malone S, Croke J, Roustan-Delatour N, Belanger E, Avruch L, Malone C, Morash C, Kayser C, Underhill K, Li Y, Malone K, Nyiri B, Spaans J (2012) Postoperative radiotherapy for prostate cancer: a comparison of four consensus guidelines and dosimetric evaluation of 3D-CRT versus tomotherapy IMRT. Int J Radiat Oncol Biol Phys 84(3):725–732. doi:10.1016/j.ijrobp.2011.12.081 CrossRefPubMed Malone S, Croke J, Roustan-Delatour N, Belanger E, Avruch L, Malone C, Morash C, Kayser C, Underhill K, Li Y, Malone K, Nyiri B, Spaans J (2012) Postoperative radiotherapy for prostate cancer: a comparison of four consensus guidelines and dosimetric evaluation of 3D-CRT versus tomotherapy IMRT. Int J Radiat Oncol Biol Phys 84(3):725–732. doi:10.​1016/​j.​ijrobp.​2011.​12.​081 CrossRefPubMed
20.
Zurück zum Zitat Sage EK, Schmid TE, Sedelmayr M, Gehrmann M, Geinitz H, Duma MN, Combs SE, Multhoff G (2016) Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. Radiother Oncol 118(1):176–180. doi:10.1016/j.radonc.2015.11.016 CrossRefPubMed Sage EK, Schmid TE, Sedelmayr M, Gehrmann M, Geinitz H, Duma MN, Combs SE, Multhoff G (2016) Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients. Radiother Oncol 118(1):176–180. doi:10.​1016/​j.​radonc.​2015.​11.​016 CrossRefPubMed
23.
Zurück zum Zitat Frey B, Rubner Y, Wunderlich R, Weiss EM, Pockley AG, Fietkau R, Gaipl US (2012) Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation – implications for cancer therapies. Curr Med Chem 19(12):1751–1764CrossRefPubMed Frey B, Rubner Y, Wunderlich R, Weiss EM, Pockley AG, Fietkau R, Gaipl US (2012) Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation – implications for cancer therapies. Curr Med Chem 19(12):1751–1764CrossRefPubMed
24.
Zurück zum Zitat Cihan YB, Arslan A, Ergul MA (2013) Subtypes of white blood cells in patients with prostate cancer or benign prostatic hyperplasia and healthy individuals. Asian Pac J Cancer Prev 14(8):4779–4783CrossRefPubMed Cihan YB, Arslan A, Ergul MA (2013) Subtypes of white blood cells in patients with prostate cancer or benign prostatic hyperplasia and healthy individuals. Asian Pac J Cancer Prev 14(8):4779–4783CrossRefPubMed
25.
Zurück zum Zitat Pinkawa M, Ribbing C, Djukic V, Klotz J, Holy R, Eble MJ (2015) Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity. Strahlenther Onkol 191(10):771–777. doi:10.1007/s00066-015-0841-3 CrossRefPubMed Pinkawa M, Ribbing C, Djukic V, Klotz J, Holy R, Eble MJ (2015) Early hematologic changes during prostate cancer radiotherapy predictive for late urinary and bowel toxicity. Strahlenther Onkol 191(10):771–777. doi:10.​1007/​s00066-015-0841-3 CrossRefPubMed
26.
Zurück zum Zitat Gershkevitsh E, Rosenberg I, Dearnaley DP, Trott KR (1999) Bone marrow doses and leukaemia risk in radiotherapy of prostate cancer. Radiother Oncol 53(3):189–197CrossRefPubMed Gershkevitsh E, Rosenberg I, Dearnaley DP, Trott KR (1999) Bone marrow doses and leukaemia risk in radiotherapy of prostate cancer. Radiother Oncol 53(3):189–197CrossRefPubMed
27.
Zurück zum Zitat Stöver I, Feyer P (2010) Praxismanual Strahlentherapie. Springer, Berlin, p 31CrossRef Stöver I, Feyer P (2010) Praxismanual Strahlentherapie. Springer, Berlin, p 31CrossRef
28.
Zurück zum Zitat Chapel H, Haeney M, Misbah S, Snowden N (2014) Essentials of clinical immunology, 6th edn. Wiley-Blackwell, Chichester Chapel H, Haeney M, Misbah S, Snowden N (2014) Essentials of clinical immunology, 6th edn. Wiley-Blackwell, Chichester
29.
Zurück zum Zitat Multhoff G, Meier T, Botzler C, Wiesnet M, Allenbacher A, Wilmanns W, Issels RD (1995) Differential effects of ifosfamide on the capacity of cytotoxic T lymphocytes and natural killer cells to lyse their target cells correlate with intracellular glutathione levels. Blood 85(8):2124–2131PubMed Multhoff G, Meier T, Botzler C, Wiesnet M, Allenbacher A, Wilmanns W, Issels RD (1995) Differential effects of ifosfamide on the capacity of cytotoxic T lymphocytes and natural killer cells to lyse their target cells correlate with intracellular glutathione levels. Blood 85(8):2124–2131PubMed
30.
Zurück zum Zitat Belka C, Ottinger H, Kreuzfelder E, Weinmann M, Lindemann M, Lepple-Wienhues A, Budach W, Grosse-Wilde H, Bamberg M (1999) Impact of localized radiotherapy on blood immune cells counts and function in humans. Radiother Oncol 50(2):199–204CrossRefPubMed Belka C, Ottinger H, Kreuzfelder E, Weinmann M, Lindemann M, Lepple-Wienhues A, Budach W, Grosse-Wilde H, Bamberg M (1999) Impact of localized radiotherapy on blood immune cells counts and function in humans. Radiother Oncol 50(2):199–204CrossRefPubMed
31.
Zurück zum Zitat Sotosek S, Sotosek Tokmadzic V, Mrakovcic-Sutic I, Tomas MI, Dominovic M, Tulic V, Sutic I, Maricic A, Sokolic J, Sustic A (2011) Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia. Wien Klin Wochenschr 123(23–24):718–725. doi:10.1007/s00508-011-0096-7 CrossRefPubMed Sotosek S, Sotosek Tokmadzic V, Mrakovcic-Sutic I, Tomas MI, Dominovic M, Tulic V, Sutic I, Maricic A, Sokolic J, Sustic A (2011) Comparative study of frequency of different lymphocytes subpopulation in peripheral blood of patients with prostate cancer and benign prostatic hyperplasia. Wien Klin Wochenschr 123(23–24):718–725. doi:10.​1007/​s00508-011-0096-7 CrossRefPubMed
32.
Zurück zum Zitat Nardone V, Botta C, Caraglia M, Martino EC, Ambrosio MR, Carfagno T, Tini P, Semeraro L, Misso G, Grimaldi A, Boccellino M, Facchini G, Berretta M, Vischi G, Rocca BJ, Barone A, Tassone P, Tagliaferri P, Del Vecchio MT, Pirtoli L, Correale P (2016) Tumor infiltrating T lymphocytes expressing FoxP3, CCR7 or PD-1 predict the outcome of prostate cancer patients subjected to salvage radiotherapy after biochemical relapse. Cancer Biol Ther. doi:10.1080/15384047.2016.1235666 PubMed Nardone V, Botta C, Caraglia M, Martino EC, Ambrosio MR, Carfagno T, Tini P, Semeraro L, Misso G, Grimaldi A, Boccellino M, Facchini G, Berretta M, Vischi G, Rocca BJ, Barone A, Tassone P, Tagliaferri P, Del Vecchio MT, Pirtoli L, Correale P (2016) Tumor infiltrating T lymphocytes expressing FoxP3, CCR7 or PD-1 predict the outcome of prostate cancer patients subjected to salvage radiotherapy after biochemical relapse. Cancer Biol Ther. doi:10.​1080/​15384047.​2016.​1235666 PubMed
33.
Zurück zum Zitat Ness N, Andersen S, Valkov A, Nordby Y, Donnem T, Al-Saad S, Busund LT, Bremnes RM, Richardsen E (2014) Infiltration of CD8+ lymphocytes is an independent prognostic factor of biochemical failure-free survival in prostate cancer. Prostate 74(14):1452–1461. doi:10.1002/pros.22862 CrossRefPubMed Ness N, Andersen S, Valkov A, Nordby Y, Donnem T, Al-Saad S, Busund LT, Bremnes RM, Richardsen E (2014) Infiltration of CD8+ lymphocytes is an independent prognostic factor of biochemical failure-free survival in prostate cancer. Prostate 74(14):1452–1461. doi:10.​1002/​pros.​22862 CrossRefPubMed
34.
Zurück zum Zitat Tao CJ, Chen YY, Jiang F, Feng XL, Jin QF, Jin T, Piao YF, Chen XZ (2016) A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy. Oncotarget 7(29):46653–46661. doi:10.18632/oncotarget.9695 PubMedPubMedCentral Tao CJ, Chen YY, Jiang F, Feng XL, Jin QF, Jin T, Piao YF, Chen XZ (2016) A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy. Oncotarget 7(29):46653–46661. doi:10.​18632/​oncotarget.​9695 PubMedPubMedCentral
35.
Zurück zum Zitat Ordonez R, Henriquez-Hernandez LA, Federico M, Valenciano A, Pinar B, Lloret M, Bordon E, Rodriguez-Gallego C, Lara PC (2014) Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients. Strahlenther Onkol 190(2):210–216. doi:10.1007/s00066-013-0488-x CrossRefPubMed Ordonez R, Henriquez-Hernandez LA, Federico M, Valenciano A, Pinar B, Lloret M, Bordon E, Rodriguez-Gallego C, Lara PC (2014) Radio-induced apoptosis of peripheral blood CD8 T lymphocytes is a novel prognostic factor for survival in cervical carcinoma patients. Strahlenther Onkol 190(2):210–216. doi:10.​1007/​s00066-013-0488-x CrossRefPubMed
36.
Zurück zum Zitat McClatchey KD (2002) Clinical laboratory medicine, 2nd edn. Lippincott Wiliams & Wilkins, Philadelphia McClatchey KD (2002) Clinical laboratory medicine, 2nd edn. Lippincott Wiliams & Wilkins, Philadelphia
Metadaten
Titel
Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients
verfasst von
Eva K. Sage
Thomas E. Schmid
Hans Geinitz
Mathias Gehrmann
Michael Sedelmayr
Marciana N. Duma
Stephanie E. Combs
Gabriele Multhoff
Publikationsdatum
12.05.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 8/2017
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-017-1144-7

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