Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy

被引:42
作者
Ohno, Akiko [1 ,2 ]
Iwata, Takashi [1 ,3 ]
Katoh, Yuki [3 ,4 ]
Taniguchi, Shiho [5 ]
Tanaka, Kohsei [1 ]
Nishio, Hiroshi [1 ]
Nakamura, Masaru [1 ]
Morisada, Tohru [1 ]
Chen, Guanliang [3 ]
Saito, Miyuki [1 ]
Yaguchi, Tomonori [3 ]
Kawakami, Yutaka [3 ,6 ]
Aoki, Daisuke [1 ]
机构
[1] Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo, Japan
[2] Natl Hosp Org Tokyo Med Ctr, Dept Obstet & Gynecol, Tokyo, Japan
[3] Keio Univ, Sch Med, Inst Adv Med Res, Div Cellular Signaling, Tokyo, Japan
[4] Nihon Univ, Sch Med, Dept Funct Morphol, Div Anat Sci, Tokyo, Japan
[5] Keio Univ, Dept Emergency & Crit Care Med, Sch Med, Tokyo, Japan
[6] Int Univ Hlth & Welf, Dept Immunol, Sch Med, Otawara, Tochigi, Japan
关键词
REGULATORY T-CELLS; ENDOTHELIAL GROWTH-FACTOR; PROGNOSTIC-FACTOR; CARCINOMA; RADIATION; IMMUNOTHERAPY; EXPRESSION; CXCL16;
D O I
10.1016/j.ygyno.2020.07.106
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objectives. To (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intratumoral abundance of various specific tumor-infiltrating lymphocytes (TILs) is a prognostic indicator in women with Stage II and III cervical cancer who undergo treatment with cisplatin-based concurrent chemoradiotherapy (CCRT), and (iii) investigate subtypes of FOXP3+ T cells in 15 fresh samples of cervical cancer. Methods. In this retrospective study, intratumoral lesions in colposcopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT at our institution were subjected to automatic immunological staining using the following six mouse monoclonal antibodies: anti-CD3, anti-CD4, anti-CD8, antiCD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and various clinicopathological characteristics were analyzed, as were associations between the abundance of various specific types of TIL and survival. Subtypes of FOXP3(+) TILs in 15 additional fresh tumor samples were also investigated using flow cytometry. Results. Infiltration with CD8(+) TILs was associated with pelvic lymph node metastasis. Abundant infiltration by CD3(+), CD4(+), CD8(+), CD206(+), and FOXP3(+) TILs were statistically significant indicators of better progressionfree and overall survival. Regarding subtypes of FOXP3(+) TILs, non-Tregs (Fr-III) were found in all samples tested for this. Conclusions. The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT. (C) 2020 Elsevier Inc. All rights reserved.
引用
收藏
页码:329 / 334
页数:6
相关论文
共 34 条
[1]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[2]   Tumor-infiltrating lymphocytes favor the response to chemoradiotherapy of head and neck cancer [J].
Balermpas, Panagiotis ;
Roedel, Franz ;
Weiss, Christian ;
Roedel, Claus ;
Fokas, Emmanouil .
ONCOIMMUNOLOGY, 2014, 3 (01)
[3]   Infiltration by immunocompetent cells in early stage invasive carcinoma of the uterine cervix: A prognostic study [J].
Bethwaite, PB ;
Holloway, LJ ;
Thornton, A ;
Delahunt, B .
PATHOLOGY, 1996, 28 (04) :321-327
[4]   Combined evaluation of the FAS cell surface death receptor and CD8+tumor infiltrating lymphocytes as a prognostic biomarker in breast cancer [J].
Blok, Erik J. ;
van den Bulk, Jitske ;
Dekker-Ensink, N. Geeske ;
Derr, Remco ;
Kanters, Corne ;
Bastiaannet, Esther ;
Kroep, Judith R. ;
van de Velde, Cornelis J. H. ;
Kuppen, Peter J. K. .
ONCOTARGET, 2017, 8 (09) :15610-15620
[5]   Tumor-infiltrating lymphocytes: apparently good for melanoma patients. But why? [J].
Cipponi, Arcadi ;
Wieers, Gregoire ;
van Baren, Nicolas ;
Coulie, Pierre G. .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2011, 60 (08) :1153-1160
[6]   The Prognostic Value of FoxP3+ Tumor-Infiltrating Lymphocytes in Cancer: A Critical Review of the Literature [J].
deLeeuw, Ronald J. ;
Kost, Sara E. ;
Kakal, Juzer A. ;
Nelson, Brad H. .
CLINICAL CANCER RESEARCH, 2012, 18 (11) :3022-3029
[7]   Prognostic factors for patients with cervical cancer treated with concurrent chemoradiotherapy: a retrospective analysis in a Japanese cohort [J].
Endo, Daisuke ;
Todo, Yukiharu ;
Okamoto, Kazuhira ;
Minobe, Shinichiro ;
Kato, Hidenori ;
Nishiyama, Noriaki .
JOURNAL OF GYNECOLOGIC ONCOLOGY, 2015, 26 (01) :12-18
[8]  
FREEMAN MR, 1995, CANCER RES, V55, P4140
[9]   High frequency of tumor-infiltrating FOXP3+ regulatory T cells predicts improved survival in mismatch repair-proficient colorectal cancer patients [J].
Frey, Daniel M. ;
Droeser, Raoul A. ;
Viehl, Carsten T. ;
Zlobec, Inti ;
Lugli, Alessandro ;
Zingg, Urs ;
Oertli, Daniel ;
Kettelhack, Christoph ;
Terracciano, Luigi ;
Tornillo, Luigi .
INTERNATIONAL JOURNAL OF CANCER, 2010, 126 (11) :2635-2643
[10]   Prognostic and Predictive Impact of Intra- and Peritumoral Immune Infiltrates [J].
Fridman, Wolf Herman ;
Galon, Jerome ;
Pages, Franck ;
Tartour, Eric ;
Sautes-Fridman, Catherine ;
Kroemer, Guido .
CANCER RESEARCH, 2011, 71 (17) :5601-5605