Abstract 3289: The status of the tumor microenvironment changes dynamics of the balance of CD8+ T cells and Treg cells in renal cell carcinoma

Immune checkpoint inhibitors (ICIs) are widely applied into the clinic based on their remarkable clinical effectiveness. Tumor mutation burden (TMB) and PD-L1 expression in the tumor microenvironment (TME) have been shown to be correlated with clinical responses of ICIs. In contrast, immunosuppressi...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.3289-3289
Hauptverfasser: Sugiyama, Daisuke, Muramatsu, Tomoaki, Kobayashi, Yoichi, Sassa, Naoto, Maruyama, Shoichi, Goto, Momokazu, Akatsuka, Yoshiki, Nishikawa, Hiroyoshi
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Sprache:eng
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Zusammenfassung:Immune checkpoint inhibitors (ICIs) are widely applied into the clinic based on their remarkable clinical effectiveness. Tumor mutation burden (TMB) and PD-L1 expression in the tumor microenvironment (TME) have been shown to be correlated with clinical responses of ICIs. In contrast, immunosuppressive cells, especially regulatory T (Treg) cells, in the TME are thought to be associated with the resistance to ICI therapy. In this study, we investigated the role of Treg cells in the TME in renal cancer (RCC). We have previously reported that the RCCs can be classified into three groups based on the frequency of CD3+CD4+CD45RA+FoxP3highcells; effector/activated Treg (eTreg) cells: high: > 10%, moderate: > 5%, and low: > 0%, and high frequency of eTreg cells were correlated with the higher expression of PD-1, LAG-3, TIM-3 by CD8+ T cells. Based on the findings, we further investigated the frequency and phenotypes of Treg cells in the TME. We first compared flow cytometry analysis with immunohistochemistry analysis in the frequency of Treg cells. The frequency of Treg cells in the TME was well-correlated with FCM and IHC analyses. Then, the detailed phenotypes of tumor-infiltrating eTreg cells was examined. eTreg cells harbored high expression of activation markers such as TIGIT and CTLA-4, but low-moderate expression of exhausted molecules such as PD-1 and LAG-3. These data implicate that CD8+ T cells are exhausted, whereas Treg cells are activated in the TME. The clinical benefits by ICI therapy for RCC could be associated with the balance of CD8+ T cells and Treg cells. We are now analyzing the detailed mechanism controlling the balance to identify biomarkers of ICI therapy and to develop novel effective cancer immunotherapies. Citation Format: Daisuke Sugiyama, Tomoaki Muramatsu, Yoichi Kobayashi, Naoto Sassa, Shoichi Maruyama, Momokazu Goto, Yoshiki Akatsuka, Hiroyoshi Nishikawa. The status of the tumor microenvironment changes dynamics of the balance of CD8+ T cells and Treg cells in renal cell carcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3289.
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2020-3289