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.
Tumor tissue from 25 ccRCC patients 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 RCC patients treated with immunotherapy (35 for training cohort and 46 for validation cohort).
In the tumor microenvironment, CD27+ T cells interacted with CD70-expressing tumor cells. Compared to CD27-T cells, CD27+ T cells exhibited an apoptotic and dysfunctional signature. In RCC patients, the intratumoral CD27-CD70 interaction was significantly correlated with the plasma soluble CD27 (sCD27) concentration. High sCD27 levels predicted poor overall survival in patients with RCC patients treated with anti-PD-1 in both the training and validation cohorts but not in patients treated with anti-angiogenic therapy.
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2022 Sep 06 [Epub ahead of print]
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, Eleonore 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, Eric Tartour
Hopital Européen Georges-Pompidou, Paris, France., INSERM U970, Paris, France., Institut Gustave Roussy, Villejuif, France., Hopital Européen Georges Pompidou, Paris, France., Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, Paris, France., Parean Biotechnologies, Saint-Malo, France., Institute Curie, PARIS, France., Institut Pasteur, Paris, France., Parean biotechnologies, Saint-Malo, France., Hopital Européen Georges Pompidou, France., Hopital Européen Georges Pompidou, Paris, FRANCE, France., Institut Pasteur, France., inserm, Paris, France., INSERM U1194, France., Mount Sinai Health System, New York, United States., AP-HP, Hopital Européen Georges Pompidou, Paris, France., Inserm, UMR-S970; Université Paris Cité, Paris, France., Institut Pasteur, Université Paris Cité, Paris, France., Institut Gustave Roussy, France., Institut Gustave Roussy, Université Paris Saclay, Villejuif, France., APHP, Paris, France., INSERM, UMR1098, Besançon cedex, France., Hopital Européen Georges Pompidou, APHP.Centre, Paris, FRANCE, France., Hopital Européen Georges Pompidou, Paris, Ile de France, France., Hopital Européen Georges-Pompidou, PARIS, France.