The following is a summary of “Plasma CD27, a Surrogate of the Intratumoral CD27–CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma” published in the November 2022 issue of Clinical Cancer by Benhamouda et al.

The costimulatory molecule CD70 is known to activate T lymphocytes that express CD27. Soluble CD27 is released due to the interaction between CD27 and CD70 (sCD27). The therapeutic implications of CD70 expression are unknown. However, clear-cell renal cell carcinoma (ccRCC) has the highest CD70 expression of all solid malignancies. Multiplex immunofluorescence was used to analyze the in situ expression of CD27 and CD70 in tumor tissue obtained from 25 individuals diagnosed with ccRCC. Flow cytometry and single-cell RNA sequencing were used to investigate the phenotypes of CD27+ T cells in malignancies, and these results were validated using publicly available information. 

About 81 individuals receiving immunotherapy for renal cell carcinoma (RCC) had their sCD27 levels checked at baseline (35 for the training cohort and 46 for validation cohort). CD27+ T cells interacted with CD70+ tumor cells in the tumor microenvironment. CD27+ T cells displayed an apoptotic and dysfunctional profile in contrast to CD27 T cells. The intratumoral CD27-CD70 interaction was substantially linked with the plasma sCD27 levels in individuals with RCC.

Patients with RCC treated with anti-programmed cell death protein 1 had high sCD27 levels predicting poor overall survival in both the training and validation groups, but patients treated with antiangiogenic treatment did not. In conclusion, their results show that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Furthermore, their results may be generalized to other malignancies due to the widespread expression of CD70 and CD27 in solid tumors.

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