Clear cell ovarian cancers with microsatellite instability: A unique subset of ovarian cancers with increased tumor-infiltrating lymphocytes and PD-1/PD-L1 expression

被引：91

作者：

Howitt, Brooke E. ^{[1
]}

Strickland, Kyle C. ^{[1
]}

Sholl, Lynette M. ^{[1
]}

Rodig, Scott ^{[1
]}

Ritterhouse, Lauren L. ^{[1
]}

Chowdhury, Dipanjan ^{[2
]}

D'Andrea, Alan D. ^{[2
]}

Matulonis, Ursula A. ^{[3
]}

Konstantinopoulos, Panagiotis A. ^{[3
]}

机构：

[1] Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Harvard Med Sch, Div Genom Stabil & DNA Repair, Boston, MA USA

[3] Harvard Med Sch, Dana Farber Canc Inst, Med Gynecol Oncol, Boston, MA USA

来源：

ONCOIMMUNOLOGY | 2017年 / 6卷 / 02期

关键词：

Clear cell ovarian cancer; immunotherapy; microsatellite instability; PD-1; PD-L1; tumor-infiltrating lymphocytes; NEOANTIGEN LOAD; ASSOCIATION; NUMBER;

D O I：

10.1080/2162402X.2016.1277308

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Clear cell ovarian carcinoma (CCOC) represents a distinct histologic subtype of ovarian cancer associated with significantly worse prognosis across all stages and no effective therapeutic options. Here, we report a rare but clinically important cohort of CCOCs with microsatellite instability (MSI) (MSI-CCOCs), which are highly immunogenic and may thus be very responsive to immune checkpoint blockade. CCOCs with MSI exhibit a significantly higher number of CD8(+) TILs, higher CD8(+)/CD4(+) ratio, and higher PD-1(+) TILs compared with microsatellite stable (MSS) CCOCs and compared with high grade serous ovarian cancers, which are the most common histologic subtype of ovarian cancer. Of note, PD-L1 expression in tumor cells or immune cells was noted in all cases of CCOCs with MSI. These observations open an alternative therapeutic avenue for a fraction of patients with CCOC and argue for the routine testing of CCOCs for MSI, a test that is not currently routinely performed.

引用

页数：4

共 10 条

[1]

[Anonymous], 47 ANN M SOC GYN ONC

[2] Lack of effective systemic therapy for recurrent clear cell carcinoma of the ovary [J].

Crotzer, David R. ;

Sun, Charlotte C. ;

Coleman, Robert L. ;

Wolf, Judith K. ;

Levenback, Charles F. ;

Gershenson, David M. .

GYNECOLOGIC ONCOLOGY, 2007, 105 (02) :404-408

[3]

Disis ML, 2015, AVELUMAB MSB0010718C

[4] Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer [J].

Hamanishi, Junzo ;

Mandai, Masaki ;

Ikeda, Takafumi ;

Minami, Manabu ;

Kawaguchi, Atsushi ;

Murayama, Toshinori ;

Kanai, Masashi ;

Mori, Yukiko ;

Matsumoto, Shigemi ;

Chikuma, Shunsuke ;

Matsumura, Noriomi ;

Abiko, Kaoru ;

Baba, Tsukasa ;

Yamaguchi, Ken ;

Ueda, Akihiko ;

Hosoe, Yuko ;

Morita, Satoshi ;

Yokode, Masayuki ;

Shimizu, Akira ;

Honjo, Tasuku ;

Konishi, Ikuo .

JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (34) :4015-+

[5] Association of Polymerase e-Mutated and Microsatellite-Instable Endometrial Cancers With Neoantigen Load, Number of Tumor-Infiltrating Lymphocytes, and Expression of PD-1 and PD-L1 [J].

Howitt, Brooke E. ;

Shukla, Sachet A. ;

Sholl, Lynette M. ;

Ritterhouse, Lauren L. ;

Watkins, Jaclyn C. ;

Rodig, Scott ;

Stover, Elizabeth ;

Strickland, Kyle C. ;

D'Andrea, Alan D. ;

Wu, Catherine J. ;

Matulonis, Ursula A. ;

Konstantinopoulos, Panagiotis A. .

JAMA ONCOLOGY, 2015, 1 (09) :1319-1323

[6] PD-1 Blockade in Tumors with Mismatch-Repair Deficiency [J].

Le, D. T. ;

Uram, J. N. ;

Wang, H. ;

Bartlett, B. R. ;

Kemberling, H. ;

Eyring, A. D. ;

Skora, A. D. ;

Luber, B. S. ;

Azad, N. S. ;

Laheru, D. ;

Biedrzycki, B. ;

Donehower, R. C. ;

Zaheer, A. ;

Fisher, G. A. ;

Crocenzi, T. S. ;

Lee, J. J. ;

Duffy, S. M. ;

Goldberg, R. M. ;

de la Chapelle, A. ;

Koshiji, M. ;

Bhaijee, F. ;

Huebner, T. ;

Hruban, R. H. ;

Wood, L. D. ;

Cuka, N. ;

Pardoll, D. M. ;

Papadopoulos, N. ;

Kinzler, K. W. ;

Zhou, S. ;

Cornish, T. C. ;

Taube, J. M. ;

Anders, R. A. ;

Eshleman, J. R. ;

Vogelstein, B. ;

Diaz, L. A., Jr. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (26) :2509-2520

[7] The Vigorous Immune Microenvironment of Microsatellite Instable Colon Cancer Is Balanced by Multiple Counter-Inhibitory Checkpoints [J].

Llosa, Nicolas J. ;

Cruise, Michael ;

Tam, Ada ;

Wicks, Elizabeth C. ;

Hechenbleikner, Elizabeth M. ;

Taube, Janis M. ;

Blosser, Richard L. ;

Fan, Hongni ;

Wang, Hao ;

Luber, Brandon S. ;

Zhang, Ming ;

Papadopoulos, Nickolas ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Sears, Cynthia L. ;

Anders, Robert A. ;

Pardoll, Drew M. ;

Housseau, Franck .

CANCER DISCOVERY, 2015, 5 (01) :43-51

[8] Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy [J].

Meng, Xiangjiao ;

Huang, Zhaoqin ;

Teng, Feifei ;

Xing, Ligang ;

Yu, Jinming .

CANCER TREATMENT REVIEWS, 2015, 41 (10) :868-876

[9] Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer [J].

Strickland, Kyle C. ;

Howitt, Brooke E. ;

Shukla, Sachet A. ;

Rodig, Scott ;

Ritterhouse, Lauren L. ;

Liu, Joyce F. ;

Garber, Judy E. ;

Chowdhury, Dipanjan ;

Wu, Catherine J. ;

D'Andrea, Alan D. ;

Matulonis, Ursula A. ;

Konstantinopoulos, Panagiotis A. .

ONCOTARGET, 2016, 7 (12) :13587-13598

[10] POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer [J].

van Gool, Inge C. ;

Eggink, Florine A. ;

Freeman-Mills, Luke ;

Stelloo, Ellen ;

Marchi, Emanuele ;

de Bruyn, Marco ;

Palles, Claire ;

Nout, Remi A. ;

de Kroon, Cor D. ;

Osse, Elisabeth M. ;

Klenerman, Paul ;

Creutzberg, Carien L. ;

Tomlinson, Ian P. M. ;

Smit, Vincent T. H. B. M. ;

Nijman, Hans W. ;

Bosse, Tjalling ;

Church, David N. .

CLINICAL CANCER RESEARCH, 2015, 21 (14) :3347-3355

← 1 →