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November 14, 2022

Plasma CD27, a Surrogate of the Intratumoral CD27–CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma

Clinical Cancer Research - 2022



Nadine Benhamouda, Ikuan Sam, Nicolas Epaillard, Alain Gey, Letuan Phan, Hang Phuong Pham, Nadège Gruel, Antonin Saldmann, Joséphine Pineau, Milena Hasan, Valentin Quiniou, Camille Nevoret, Virginie Verkarre, Valentina Libri, Sebastien Mella, Clémence Granier, Chloe Broudin, Patrice Ravel, Eléonore De Guillebon, Laetitia Mauge, Dominique Helley, Bernd Jabla, Nathalie Chaput, Laurence Albiges, Sandrine Katsahian, Julien Adam, Arnaud Mejean, Olivier Adotevi, Yann A. Vano, Stéphane Oudard, and Eric Tartour.

  • puce

    Purpose: CD70 is a costimulatory molecule known to activate CD27-expressing T cells. CD27–CD70 interaction leads to the release of soluble CD27 (sCD27). Clear-cell renal cell carcinoma (ccRCC) expresses the highest levels of CD70 among all solid tumors; however, the clinical consequences of CD70 expression remain unclear.

  • puce

    Experimental Design: Tumor tissue from 25 patients with ccRCC was assessed for the expression of CD27 and CD70 in situ using multiplex immunofluorescence. CD27+ T-cell phenotypes in tumors were analyzed by flow cytometry and their gene expression profile were analyzed by single-cell RNA sequencing then confirmed with public data. Baseline sCD27 was measured in 81 patients with renal cell carcinoma (RCC) treated with immunotherapy (35 for training cohort and 46 for validation cohort).

  • puce

    Results: In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared with CD27 T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In patients with RCC, the intratumoral CD27–CD70 interaction was significantly correlated with the plasma sCD27 concentration. High sCD27 levels predicted poor overall survival in patients with RCC treated with anti–programmed cell death protein 1 in both the training and validation cohorts but not in patients treated with antiangiogenic therapy.

  • puce

    Conclusions: In conclusion, we demonstrated that sCD27, a surrogate marker of T-cell dysfunction, is a predictive biomarker of resistance to immunotherapy in RCC. Given the frequent expression of CD70 and CD27 in solid tumors, our findings may be extended to other tumors.

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