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Relationship of B7-H3 expression in tumor cells and tumor vasculature with FOXP3+ regulatory T cells in renal cell carcinoma

Authors Inamura K, Amori G, Yuasa T, Yamamoto S, Yonese J, Ishikawa Y

Received 19 March 2019

Accepted for publication 15 July 2019

Published 25 July 2019 Volume 2019:11 Pages 7021—7030

DOI https://doi.org/10.2147/CMAR.S209205

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Professor Nakshatri


Kentaro Inamura,1,2 Gulanbar Amori,1,2 Takeshi Yuasa,3 Shinya Yamamoto,3 Junji Yonese,3 Yuichi Ishikawa1,2

1Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan; 2Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; 3Department of Urology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan

Background: B7-H3 (CD276), an immune checkpoint molecule, regulates the tumor-immune microenvironment and controls the aggressiveness of various tumors. Although B7-H3 expression has been associated with the number of tumor-infiltrating FOXP3+ regulatory T cells, little information is available about this association in clear cell renal cell carcinoma (ccRCC).
Methods: Using 252 consecutive cases of ccRCC, we examined the association of B7-H3 expression in both the tumor cells and tumor vasculature with the number of tumor-infiltrating FOXP3+ cells and assessed whether the effects of B7-H3 expression on survival differ according to FOXP3+ cell number.
Results: High B7-H3 expression was observed in the tumor cells and tumor vasculature in 15% and 54% of ccRCC cases, respectively. High FOXP3+ cell number was positively associated with B7-H3 expression in both the tumor cells (odds ratio [OR] =2.93; P=0.0041) and tumor vasculature (OR=2.45; P=0.0007). Tumor cell B7-H3 expression was associated with increased disease-specific mortality in high FOXP3+ cell number group (hazard ratio [HR] =2.98; P=0.017), but not in low FOXP3+ group (P=0.71). Tumor vasculature B7-H3 expression was also associated with increased disease-specific mortality in high FOXP3+ cell number group (HR=4.86; P=0.0025), but not in low FOXP3+ group (P=0.48).
Conclusion: We demonstrate that B7-H3 expression in both tumor cells and the tumor vasculature is positively associated with FOXP3+ cell number. Such expression is also associated with increased mortality in high FOXP3+ cell number group, but not in low FOXP3+ cell number group. These findings suggest that B7-H3-expressing ccRCCs may exert tumor-promoting immunity by interacting with FOXP3+ regulatory T cells in the tumor microenvironment.

Keywords: immune checkpoint inhibitor, immunotherapy, prognosis, renal cancer, TIL

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