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Prognostic impact of CD73/adenosine 2A receptor (A2AR) in renal cell carcinoma and immune microenvironmental status
Dai Takamatsu1, Daisuke Kiyozawa1, Kenichi Kohashi1
1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abstract:
One of the most aggressive forms of kidney cancer is renal cell carcinoma (RCC) with sarcomatoid changes and rhabdoid features (S/R). Adenosine produced via CD73 binds to adenosine 2 A receptor (A2AR) and suppress antitumor immunity. Here, we attempted to analyze the expression of CD73/A2AR in S/R RCC and examined its relationships with other immune microenvironments and prognostic effect. Sixty cases of S/R RCC were selected. CD73/A2AR expression levels were graded in the tumor cells or infiltrating immune cells on a score of 0-3 and divided into low (0 or 1) or high (2 or 3) groups. PD-L1 results were defined by the tumor proportion score (TPS). We counted the numbers of CD8+, FOXP3+, CD68+, and CD163+ immune cells. The rates of CD73/A2AR expression in epithelial component (23.3% and 15.0%) were lower than those in high-grade component (70.0% and 45.0%). CD73/A2AR were significantly correlated to high numbers of regulatory Tcells and macrophages of M2 subtype (CD73: P = 0.0059 and 0.0002; A2AR: P = 0.0002 and 0.018, respectively). Multivariate analysis showed that CD73/A2AR expressions were independent markers of unfavorable prognosis in S/R RCCs (P = 0.0204 and 0.0116, respectively). In RCC, the S/R component had higher expressions of CD73/A2AR than the epithelial component, and CD73/A2AR were independent prognostic factors. Compared with other RCCs, S/R RCCs are more effective at blocking adenosine signaling and CD73/A2AR inhibitors are expected to enhance the therapeutic efficacy and improve the prognosis of immune checkpoint inhibitor therapies.
Insights
High expression of CD73 and adenosine 2A receptor (A2AR) in aggressive renal cell carcinoma (RCC) with sarcomatoid/rhabdoid features (S/R) correlates with poor prognosis. Targeting CD73/A2AR may improve immunotherapy efficacy in S/R RCC.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Renal cell carcinoma (RCC) with sarcomatoid and rhabdoid features (S/R) is an aggressive cancer subtype.
- Adenosine signaling via CD73 and adenosine 2A receptor (A2AR) suppresses antitumor immunity.
- Understanding CD73/A2AR expression in S/R RCC is crucial for developing targeted therapies.
Purpose of the Study:
- To analyze CD73/A2AR expression in S/R RCC.
- To investigate the relationship between CD73/A2AR and the tumor immune microenvironment.
- To determine the prognostic significance of CD73/A2AR in S/R RCC.
Main Methods:
- Sixty S/R RCC cases were analyzed for CD73/A2AR expression.
- Immune cell infiltration (CD8+, FOXP3+, CD68+, CD163+) was quantified.
- Correlation and multivariate analyses were performed to assess prognostic impact.
Main Results:
- S/R RCC components showed higher CD73/A2AR expression than epithelial components.
- CD73/A2AR expression correlated with increased regulatory T cells and M2 macrophages.
- High CD73/A2AR expression was an independent marker of unfavorable prognosis in S/R RCC.
Conclusions:
- CD73/A2AR are upregulated in the aggressive S/R component of RCC.
- CD73/A2AR expression is linked to an immunosuppressive tumor microenvironment.
- Inhibiting CD73/A2AR may enhance immunotherapy outcomes for S/R RCC patients.
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