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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

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Tumor Biology

Abstract

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.

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    Authors and Affiliations

    1. Department of Anesthesiology, The Maternal and Child Health Hospital of Jinan City, Jinan, Shandong, 250001, China

      Meimei Bu, Shizhi An & Rongqin Qi

    2. Department of Urology, General Hospital of Jinan Military Command, Jinan, Shandong, 250031, China

      Yizhen Shen

    3. Research Center, Lingbin Biotechnology, Surrey, BC, Canada

      William L. Seeger & Joanna A. Sanderson

    4. 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

      Yan Cai

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    1. Meimei Bu
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    2. Yizhen Shen
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    Correspondence to Yan Cai.

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    Meimei Bu and Yizhen Shen contributed equally to this work.

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    Bu, M., Shen, Y., Seeger, W.L. et al. 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. Tumor Biol. 37, 3949–3956 (2016). https://doi.org/10.1007/s13277-015-4237-x

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    • DOI: https://doi.org/10.1007/s13277-015-4237-x

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