Post-chemotherapy T-cell recovery is a marker of improved survival in patients with advanced thoracic malignancies

被引:59
作者
Mccoy, M. J. [1 ,2 ]
Lake, R. A. [1 ,2 ]
van der Most, R. G. [1 ,2 ]
Dick, I. M. [1 ,2 ]
Nowak, A. K. [1 ,2 ,3 ]
机构
[1] Univ Western Australia, Sch Med & Pharmacol, Tumour Immunol Grp, Perth, WA 6009, Australia
[2] Natl Ctr Asbestos Related Dis, Perth, WA, Australia
[3] Sir Charles Gairdner Hosp, Dept Med Oncol, Perth, WA 6009, Australia
基金
英国医学研究理事会;
关键词
chemotherapy; mesothelioma; non-small cell lung cancer; T cells; prognosis; PLEURAL MESOTHELIOMA; IMMUNE-RESPONSE; LUNG-CANCER; IN-VIVO; ANTITUMOR IMMUNITY; MELANOMA PATIENTS; PROGNOSTIC MODEL; TUMOR-IMMUNITY; SOLID TUMORS; PHASE-III;
D O I
10.1038/bjc.2012.362
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND: There is increasing interest in combining chemotherapy with immunotherapy. However, the effects of chemotherapy on the human immune system are largely unknown. METHODS: Longitudinal changes in peripheral T-cell subsets in 40 patients with malignant mesothelioma (MM) or advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy were assessed by flow cytometry and evaluated for associations with clinical outcome. RESULTS: Proliferating T cells of all subsets were almost entirely depleted at day 8 following chemotherapy, but rapidly recovered above baseline levels. Regulatory T cells (Treg) were most profoundly depleted at this time point. A greater increase in CD8(+) T-cell proliferation following one treatment cycle was associated with improved overall survival in univariate (hazard ratio (HR) = 0.40; P < 0.05) and multivariate (HR = 0.17; P < 0.01) analyses. A greater increase in the ratio of CD8(+) T cell to Treg proliferation was also predictive of better prognosis. CONCLUSION: Chemotherapy potentially provides a favourable environment for the development of anti-tumour immunity through transient Treg depletion and regeneration of the T-cell pool. Change in CD8(+) T-cell proliferation after one cycle of chemotherapy may represent a useful prognostic indicator in patients with MM and NSCLC. British Journal of Cancer (2012) 107, 1107-1115. doi:10.1038/bjc.2012.362 www.bjcancer.com Published online 21 August 2012 (c) 2012 Cancer Research UK
引用
收藏
页码:1107 / 1115
页数:9
相关论文
共 53 条
[41]   Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer [J].
Scagliotti, Giorgio Vittorio ;
Parikh, Purvish ;
von Pawel, Joachim ;
Biesma, Bonne ;
Vansteenkiste, Johan ;
Manegold, Christian ;
Serwatowski, Piotr ;
Gatzemeier, Ulrich ;
Digumarti, Raghunadharao ;
Zukin, Mauro ;
Lee, Jin S. ;
Mellemgaard, Anders ;
Park, Keunchil ;
Patil, Shehkar ;
Rolski, Janusz ;
Goksel, Tuncay ;
de Marinis, Filippo ;
Simms, Lorinda ;
Sugarman, Katherine P. ;
Gandara, David .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (21) :3543-3551
[42]   Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer [J].
Schiller, JH ;
Harrington, D ;
Belani, CP ;
Langer, C ;
Sandler, A ;
Krook, J ;
Zhu, JM ;
Johnson, DH .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (02) :92-98
[43]   Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo [J].
Schluns, KS ;
Kieper, WC ;
Jameson, SC ;
Lefrançois, L .
NATURE IMMUNOLOGY, 2000, 1 (05) :426-432
[44]   Persistence of naive CD45RA+ regulatory T cells in adult life [J].
Seddiki, N ;
Santner-Nanan, B ;
Tangye, SG ;
Alexander, SI ;
Solomon, M ;
Lee, S ;
Nanan, R ;
Fazekas de St Groth, B .
BLOOD, 2006, 107 (07) :2830-2838
[45]   Immunomodulatory effects of cyclophosphamide and implementations for vaccine design [J].
Sistigu, Antonella ;
Viaud, Sophie ;
Chaput, Nathalie ;
Bracci, Laura ;
Proietti, Enrico ;
Zitvogel, Laurence .
SEMINARS IN IMMUNOPATHOLOGY, 2011, 33 (04) :369-383
[46]   Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells [J].
Tan, JT ;
Ernst, B ;
Kieper, WC ;
LeRoy, E ;
Sprent, J ;
Surh, CD .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 195 (12) :1523-1532
[47]  
Therasse P, 2000, J NATL CANCER I, V92, P205, DOI 10.1093/jnci/92.3.205
[48]   Pretreatment with cisplatin enhances E7-specific CD8+ T-cell mediated antitumor immunity induced by DNA vaccination [J].
Tseng, Chih-Wen ;
Hung, Chien-Fu ;
Alvarez, Ronald D. ;
Trimble, Cornelia ;
Huh, Warner K. ;
Kim, Daejin ;
Chuang, Chi-Mu ;
Lin, Cheng-Tao ;
Tsai, Ya-Chea ;
He, Liangmei ;
Monie, Archana ;
Wu, T-C. .
CLINICAL CANCER RESEARCH, 2008, 14 (10) :3185-3192
[49]   Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy [J].
van der Most, Robbert G. ;
Currie, Andrew J. ;
Mahendran, Sathish ;
Prosser, Amy ;
Darabi, Anna ;
Robinson, Bruce W. S. ;
Nowak, Anna K. ;
Lake, Richard A. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2009, 58 (08) :1219-1228
[50]   Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma [J].
Vogelzang, NJ ;
Rusthoven, JJ ;
Symanowski, J ;
Denham, C ;
Kaukel, E ;
Ruffie, P ;
Gatzemeier, U ;
Boyer, M ;
Emri, S ;
Manegold, C ;
Niyikiza, C ;
Paoletti, P .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (14) :2636-2644