Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression.
Ovarian carcinoma is one of the most severe cancers in women, with a high relapse rate and limited secondary treatment options. To assist research in novel treatment technologies, including CD8(+) T cell-base immunotherapy, we examined the effect of tumor-infiltrating regulatory T cells (Tregs) in inhibiting CD8(+) T cell inflammation. We found that compared to their peripheral blood counterparts, tumor-infiltrating Tregs exhibited more potent inhibitory function, which was associated with higher interleukin 10 (IL-10) production in tumor-infiltrating Tregs. Blockade of T cell immunoglobulin mucin 3 (TIM3), a regulatory molecule overrepresented on tumor-infiltrating Tregs, had significantly reverted Treg-mediated suppression. Moreover, expression of TIM3 on tumor-infiltrating Tregs was directly correlated with tumor size. Together, our results demonstrated that ovarian tumor-infiltrating Treg cells were more immunosuppressive than their peripheral blood counterparts in a TIM3-dependent fashion.
Department of Anesthesiology, The Maternal and Child Health Hospital of Jinan City, Jinan, Shandong, 250001, China.
Meimei
M
Bu
Department of Urology, General Hospital of Jinan Military Command, Jinan, Shandong, 250031, China.
Yizhen
Y
Shen
Research Center, Lingbin Biotechnology, Surrey, BC, Canada.
William L
WL
Seeger
Department of Anesthesiology, The Maternal and Child Health Hospital of Jinan City, Jinan, Shandong, 250001, China.
Shizhi
S
An
Department of Anesthesiology, The Maternal and Child Health Hospital of Jinan City, Jinan, Shandong, 250001, China.
Rongqin
R
Qi
Research Center, Lingbin Biotechnology, Surrey, BC, Canada.
Joanna A
JA
Sanderson
Department of Prenatal Diagnosis, The Maternal and Child Health Hospital of Jinan City, No.2 Jian Guo Xiao Jing San Road, Jinan, Shandong, 250001, China. yancai_jn@sina.com.
Yan
Y
Cai
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000096:biosynthesis; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D047368:Tumor Burden
C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C508609:IL10 protein, human; D016753:Interleukin-10
Ovarian cancer; Regulatory T cell; TIM3; Tumor-infiltrating lymphocyte