Clarice S Groeneveld1, Jacqueline Fontugne2, Luc Cabel3, Isabelle Bernard-Pierrot3, François Radvanyi3, Yves Allory2, Aurélien de Reyniès4. 1. Cartes d'Identité des Tumeurs (CIT) Program, Ligue Nationale Contre le Cancer, Paris, France; Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France. 2. Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France; Department of Pathology, Institut Curie, Saint-Cloud, France. 3. Molecular Oncology, PSL Research University, CNRS, UMR 144, Institut Curie, Equipe Labellisée Ligue Nationale Contre le Cancer, Paris, France. 4. Cartes d'Identité des Tumeurs (CIT) Program, Ligue Nationale Contre le Cancer, Paris, France. Electronic address: aurelien.dereynies@ligue-cancer.net.
Abstract
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have proved to be an effective treatment for up to 40% of muscle-invasive bladder cancer (MIBC), but there is still a need for better performing biomarkers allowing to improve prediction of response to ICI. Response to immunotherapy in soft-tissue sarcoma, melanoma and renal cell carcinoma have been recently linked to the presence of tertiary lymphoid structures (TLS) in the tumour. TLS are organised aggregates of T, B and dendritic cells, participating in adaptive antitumor immune response. The chemokine CXCL13 is involved in the formation of TLS, and is reported as a reliable transcriptomic marker of TLS. OBJECTIVES: In this study, we sought to assess whether CXCL13 transcript expression can be a prognostic biomarker for ICI-treated MIBC patients and also investigated whether it can serve a biomarker of TLS in MIBC. METHODS: We analysed transcriptomic data from three publicly available MIBC cohorts and evaluated pathological slides from the TCGA-BLCA cohort for TLS presence and stage of maturation. RESULTS: We showed that CXCL13 was independently associated with both prolonged survival (HR = 0.8, 95% CI [0.68-0.94]) and objective response (p < 0.0001) in patients treated with ICI, at the difference of others immunological signatures. However, it was not a predictor for non-ICI-treated MIBC, suggesting a predictive effect of ICI efficacy. Finally, we validated that CXCL13 expression was correlated with tumour TLS in TCGA data set (p < 0.001), and can serve as a marker of TLS in bladder cancer. CONCLUSION: These results support that CXCL13 expression, as a surrogate for tumour TLS, is a relevant candidate predictive biomarker of response to ICI for patients with advanced-stage bladder cancer.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have proved to be an effective treatment for up to 40% of muscle-invasive bladder cancer (MIBC), but there is still a need for better performing biomarkers allowing to improve prediction of response to ICI. Response to immunotherapy in soft-tissue sarcoma, melanoma and renal cell carcinoma have been recently linked to the presence of tertiary lymphoid structures (TLS) in the tumour. TLS are organised aggregates of T, B and dendritic cells, participating in adaptive antitumor immune response. The chemokine CXCL13 is involved in the formation of TLS, and is reported as a reliable transcriptomic marker of TLS. OBJECTIVES: In this study, we sought to assess whether CXCL13 transcript expression can be a prognostic biomarker for ICI-treated MIBCpatients and also investigated whether it can serve a biomarker of TLS in MIBC. METHODS: We analysed transcriptomic data from three publicly available MIBC cohorts and evaluated pathological slides from the TCGA-BLCA cohort for TLS presence and stage of maturation. RESULTS: We showed that CXCL13 was independently associated with both prolonged survival (HR = 0.8, 95% CI [0.68-0.94]) and objective response (p < 0.0001) in patients treated with ICI, at the difference of others immunological signatures. However, it was not a predictor for non-ICI-treated MIBC, suggesting a predictive effect of ICI efficacy. Finally, we validated that CXCL13 expression was correlated with tumour TLS in TCGA data set (p < 0.001), and can serve as a marker of TLS in bladder cancer. CONCLUSION: These results support that CXCL13 expression, as a surrogate for tumour TLS, is a relevant candidate predictive biomarker of response to ICI for patients with advanced-stage bladder cancer.
Authors: Amit I Bery; Hailey M Shepherd; Wenjun Li; Alexander S Krupnick; Andrew E Gelman; Daniel Kreisel Journal: Cell Mol Life Sci Date: 2022-06-11 Impact factor: 9.207
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