Investigating the complex interplay between fibroblast activation protein α-positive cancer associated fibroblasts and the tumor microenvironment in the context of cancer immunotherapy.

Autor:	Kraxner A; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Braun F; Roche Pharma Research and Early Development, Data and Analytics, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany., Cheng WY; Roche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd, Little Falls, NJ, United States., Yang TO; Roche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd, Little Falls, NJ, United States., Pipaliya S; Roche Pharma Research and Early Development, Data and Analytics, Roche Innovation Center Zurich, Roche Glycart AG, Schlieren, Switzerland., Canamero M; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany., Andersson E; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany., Harring SV; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany., Dziadek S; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Bröske AE; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany., Ceppi M; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Tanos T; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Teichgräber V; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland., Charo J; Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Zurich, Roche Glycart AG, Schlieren, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jul 05; Vol. 15, pp. 1352632. Date of Electronic Publication: 2024 Jul 05 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1352632
Abstrakt:	Introduction: This study investigates the role of Fibroblast Activation Protein (FAP)-positive cancer-associated fibroblasts (FAP+CAF) in shaping the tumor immune microenvironment, focusing on its association with immune cell functionality and cytokine expression patterns. Methods: Utilizing immunohistochemistry, we observed elevated FAP+CAF density in metastatic versus primary renal cell carcinoma (RCC) tumors, with higher FAP+CAF correlating with increased T cell infiltration in RCC, a unique phenomenon illustrating the complex interplay between tumor progression, FAP+CAF density, and immune response. Results: Analysis of immune cell subsets in FAP+CAF-rich stromal areas further revealed significant correlations between FAP+ stroma and various T cell types, particularly in RCC and non-small cell lung cancer (NSCLC). This was complemented by transcriptomic analyses, expanding the range of stromal and immune cell subsets interrogated, as well as to additional tumor types. This enabled evaluating the association of these subsets with tumor infiltration, tumor vascularization and other components of the tumor microenvironment. Our comprehensive study also encompassed cytokine, angiogenesis, and inflammation gene signatures across different cancer types, revealing heterogeneous cellular composition, cytokine expressions and angiogenic profiles. Through cytokine pathway profiling, we explored the relationship between FAP+CAF density and immune cell states, uncovering potential immunosuppressive circuits that limit anti-tumor activity in tumor-resident immune cells. Conclusions: These findings underscore the complexity of tumor biology and the necessity for personalized therapeutic and patient enrichment approaches. The insights gathered from FAP+CAF prevalence, immune infiltration, and gene signatures provide valuable perspectives on tumor microenvironments, aiding in future research and clinical strategy development. Competing Interests: Authors are paid employees and stockholders of Hoffman- LA Roche AG, Basel, Switzerland (Copyright © 2024 Kraxner, Braun, Cheng, Yang, Pipaliya, Canamero, Andersson, Harring, Dziadek, Bröske, Ceppi, Tanos, Teichgräber and Charo.)
Databáze:	MEDLINE
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