Article ; Online: Plasma CD27, a Surrogate of the Intratumoral CD27-CD70 Interaction, Correlates with Immunotherapy Resistance in Renal Cell Carcinoma.
Clinical cancer research : an official journal of the American Association for Cancer Research
2022 Volume 28, Issue 22, Page(s) 4983–4994
Abstract: 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; ...
| Abstract | 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. 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). 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. 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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| MeSH term(s) | Humans ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; CD27 Ligand/genetics ; Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics ; Immunotherapy ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Tumor Microenvironment | |||||
| Chemical Substances | CD27 Ligand ; Tumor Necrosis Factor Receptor Superfamily, Member 7 ; CD70 protein, human | |||||
| Language | English | |||||
| Publishing date | 2022-09-06 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 1225457-5 | |||||
| ISSN | 1557-3265 ; 1078-0432 | |||||
| ISSN (online) | 1557-3265 | |||||
| ISSN | 1078-0432 | |||||
| DOI | 10.1158/1078-0432.CCR-22-0905 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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