Tertiary lymphoid structures are associated with favorable survival outcomes in patients with endometrial cancer

被引:31
作者
Qin, Meng [1 ,2 ]
Hamanishi, Junzo [1 ]
Ukita, Masayo [1 ]
Yamanoi, Koji [1 ]
Takamatsu, Shiro [1 ]
Abiko, Kaoru [1 ,3 ]
Murakami, Ryusuke [1 ,4 ]
Miyamoto, Taito [1 ]
Suzuki, Haruka [1 ]
Ueda, Akihiko [1 ]
Hosoe, Yuko [1 ]
Horie, Akihito [1 ]
Yamaguchi, Ken [1 ]
Mandai, Masaki [1 ]
机构
[1] Kyoto Univ, Dept Gynecol & Obstet, Grad Sch Med, Sakyo Ku, 54 Kawaharacho, Kyoto 6068507, Japan
[2] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China
[3] Natl Hosp Org Kyoto Med Ctr, Dept Obstet & Gynecol, Kyoto, Japan
[4] Shiga Gen Hosp, Dept Gynecol, Moriyama, Shiga, Japan
关键词
Tertiary lymphoid structures; B cells; Endometrial cancer; Survival outcomes; Immunohistochemistry; Immune response; PROGRAMMED CELL-DEATH-1; PROGNOSTIC RELEVANCE; IMMUNE-RESPONSE; B-CELLS; IMMUNOTHERAPY; BREAST;
D O I
10.1007/s00262-021-03093-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Immunotherapy has experienced remarkable growth recently. Tertiary lymphoid structures (TLSs) and B cells may play a key role in the immune response and have a survival benefit in some solid tumors, but there have been no reports about their role in endometrial cancer (EC). We investigated the clinicopathological and pathobiological characteristics of the tumor microenvironment (TME) in EC. Patients with EC at Kyoto University Hospital during 2006-2011 were retrospectively included. In 104 patients with EC who met study inclusion criteria, 81 (77.9%) had TLSs, which consisted of areas rich in CD20(+) B cells, CD8(+) T cells, CD4(+) T cells, and CD38(+) plasma cells. The absence of TLS was independently associated with tumor progression (HR, 0.154; 95% CI, 0.044-0.536; P = 0.003). Patients with TLSs that included CD23(+) germinal centers had better PFS. All tumor infiltrating lymphocytes were counted in the intratumor site. The number of CD20(+) B cells was significantly larger in patients with TLSs than in those without TLS (P < 0.001). CD20(+) B cells numbers were positively correlated with other TLSs. The larger number of CD20(+) B cell was associated with better PFS (P = 0.015). TLSs and B cell infiltration into tumors are associated with favorable survival outcomes in patients with EC. They may represent an active immune reaction of the TME in endometrial cancer.
引用
收藏
页码:1431 / 1442
页数:12
相关论文
共 42 条
[1]   Understanding high endothelial venules: Lessons for cancer immunology [J].
Ager, Ann ;
May, Michael J. .
ONCOIMMUNOLOGY, 2015, 4 (06)
[2]  
[Anonymous], 2015, Obstet Gynecol, V125, P1272, DOI 10.1097/01.AOG.0000465189.50026.20
[3]   Tertiary lymphoid structures improve immunotherapy and survival in melanoma [J].
Cabrita, Rita ;
Lauss, Martin ;
Sanna, Adriana ;
Donia, Marco ;
Larsen, Mathilde Skaarup ;
Mitra, Shamik ;
Johansson, Iva ;
Phung, Bengt ;
Harbst, Katja ;
Vallon-Christersson, Johan ;
van Schoiack, Alison ;
Loevgren, Kristina ;
Warren, Sarah ;
Jirstroem, Karin ;
Olsson, Hakan ;
Pietras, Kristian ;
Ingvar, Christian ;
Isaksson, Karolin ;
Schadendorf, Dirk ;
Schmidt, Henrik ;
Bastholt, Lars ;
Carneiro, Ana ;
Wargo, Jennifer A. ;
Svane, Inge Marie ;
Jonsson, Goran .
NATURE, 2020, 577 (7791) :561-+
[4]   Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study [J].
Chung, Hyun Cheol ;
Ros, Willeke ;
Delord, Jean-Pierre ;
Perets, Ruth ;
Italiano, Antoine ;
Shapira-Frommer, Ronnie ;
Manzuk, Lyudmila ;
Piha-Paul, Sarina A. ;
Xu, Lei ;
Zeigenfuss, Susan ;
Pruitt, Scott K. ;
Leary, Alexandra .
JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (17) :1470-+
[5]   Characterization of Chemokines and Adhesion Molecules Associated with T cell Presence in Tertiary Lymphoid Structures in Human Lung Cancer [J].
de Chaisemartin, Luc ;
Goc, Jeremy ;
Damotte, Diane ;
Validire, Pierre ;
Magdeleinat, Pierre ;
Alifano, Marco ;
Cremer, Isabelle ;
Fridman, Wolf-Herman ;
Sautes-Fridman, Catherine ;
Dieu-Nosjean, Marie-Caroline .
CANCER RESEARCH, 2011, 71 (20) :6391-6399
[6]   Occurrence of Tertiary Lymphoid Tissue Is Associated with T-Cell Infiltration and Predicts Better Prognosis in Early-Stage Colorectal Cancers [J].
Di Caro, Giuseppe ;
Bergomas, Francesca ;
Grizzi, Fabio ;
Doni, Andrea ;
Bianchi, Paolo ;
Malesci, Alberto ;
Laghi, Luigi ;
Allavena, Paola ;
Mantovani, Alberto ;
Marchesi, Federica .
CLINICAL CANCER RESEARCH, 2014, 20 (08) :2147-2158
[7]   Immunotherapy in endometrial cancer: new scenarios on the horizon [J].
Di Tucci, Chiara ;
Capone, Carmela ;
Galati, Giulia ;
Iacobelli, Valentina ;
Schiavi, Michele C. ;
Di Donato, Violante ;
Muzii, Ludovico ;
Panici, Pierluigi Benedetti .
JOURNAL OF GYNECOLOGIC ONCOLOGY, 2019, 30 (03)
[8]   Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures [J].
Dieu-Nosjean, Marie-Caroline ;
Antoine, Martine ;
Danel, Claire ;
Heudes, Didier ;
Wislez, Marie ;
Poulot, Virginie ;
Rabbe, Nathalie ;
Laurans, Ludivine ;
Tartour, Eric ;
de Chaisemartin, Luc ;
Lebecque, Serge ;
Fridman, Wolf-Herman ;
Cadranel, Jacques .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (27) :4410-4417
[9]   Proteogenomic Characterization of Endometrial Carcinoma [J].
Dou, Yongchao ;
Kawaler, Emily A. ;
Zhou, Daniel Cui ;
Gritsenko, Marina A. ;
Huang, Chen ;
Blumenberg, Lili ;
Karpova, Alla ;
Petyuk, Vladislav A. ;
Savage, Sara R. ;
Satpathy, Shankha ;
Liu, Wenke ;
Wu, Yige ;
Tsai, Chia-Feng ;
Wen, Bo ;
Li, Zhi ;
Cao, Song ;
Moon, Jamie ;
Shi, Zhiao ;
Cornwell, MacIntosh ;
Wyczalkowski, Matthew A. ;
Chu, Rosalie K. ;
Vasaikar, Suhas ;
Zhou, Hua ;
Gao, Qingsong ;
Moore, Ronald J. ;
Li, Kai ;
Sethuraman, Sunantha ;
Monroe, Matthew E. ;
Zhao, Rui ;
Heiman, David ;
Krug, Karsten ;
Clauser, Karl ;
Kothadia, Ramani ;
Maruvka, Yosef ;
Pico, Alexander R. ;
Oliphant, Amanda E. ;
Hoskins, Emily L. ;
Pugh, Samuel L. ;
Beecroft, Sean J. I. ;
Adams, David W. ;
Jarman, Jonathan C. ;
Kong, Andy ;
Chang, Hui-Yin ;
Reva, Boris ;
Liao, Yuxing ;
Rykunov, Dmitry ;
Colaprico, Antonio ;
Chen, Xi Steven ;
Czekanski, Andrzej ;
Jedryka, Marcin .
CELL, 2020, 180 (04) :729-+
[10]   Choosing Statistical Tests [J].
du Prel, Jean-Baptist ;
Roehrig, Bernd ;
Hommel, Gerhard ;
Blettner, Maria .
DEUTSCHES ARZTEBLATT INTERNATIONAL, 2010, 107 (19) :343-348