Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma.

Autor:	Zhang H; Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., AbdulJabbar K; Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Moore DA; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom.; Department of Cellular Pathology, University College London Hospitals, London, United Kingdom., Akarca A; Department of Cellular Pathology, University College London Hospitals, London, United Kingdom., Enfield KSS; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom., Jamal-Hanjani M; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom.; Department of Oncology, University College London Hospitals, London, United Kingdom.; Cancer Metastasis Lab, University College London Cancer Institute, London, United Kingdom., Raza SEA; Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom., Veeriah S; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom., Salgado R; Department of Pathology, ZAS Hospitals, Antwerp, Belgium., McGranahan N; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom.; Cancer Genome Evolution Research Group, Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom., Le Quesne J; Cancer Research UK Beatson Institute, Glasgow, United Kingdom.; School of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.; NHS Greater Glasgow and Clyde Pathology Department, Queen Elizabeth University Hospital, London, United Kingdom., Swanton C; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, United Kingdom.; Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom.; Department of Oncology, University College London Hospitals, London, United Kingdom., Marafioti T; Department of Cellular Pathology, University College London Hospitals, London, United Kingdom., Yuan Y; Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.; Division of Molecular Pathology, The Institute of Cancer Research, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2023 May 02; Vol. 83 (9), pp. 1410-1425.
DOI:	10.1158/0008-5472.CAN-22-2589
Abstrakt:	Beyond tertiary lymphoid structures, a significant number of immune-rich areas without germinal center-like structures are observed in non-small cell lung cancer. Here, we integrated transcriptomic data and digital pathology images to study the prognostic implications, spatial locations, and constitution of immune rich areas (immune hotspots) in a cohort of 935 patients with lung cancer from The Cancer Genome Atlas. A high intratumoral immune hotspot score, which measures the proportion of immune hotspots interfacing with tumor islands, was correlated with poor overall survival in lung squamous cell carcinoma but not in lung adenocarcinoma. Lung squamous cell carcinomas with high intratumoral immune hotspot scores were characterized by consistent upregulation of B-cell signatures. Spatial statistical analyses conducted on serial multiplex IHC slides further revealed that only 4.87% of peritumoral immune hotspots and 0.26% of intratumoral immune hotspots were tertiary lymphoid structures. Significantly lower densities of CD20+CXCR5+ and CD79b+ B cells and less diverse immune cell interactions were found in intratumoral immune hotspots compared with peritumoral immune hotspots. Furthermore, there was a negative correlation between the percentages of CD8+ T cells and T regulatory cells in intratumoral but not in peritumoral immune hotspots, with tertiary lymphoid structures excluded. These findings suggest that the intratumoral immune hotspots reflect an immunosuppressive niche compared with peritumoral immune hotspots, independent of the distribution of tertiary lymphoid structures. A balance toward increased intratumoral immune hotspots is indicative of a compromised antitumor immune response and poor outcome in lung squamous cell carcinoma. Significance: Intratumoral immune hotspots beyond tertiary lymphoid structures reflect an immunosuppressive microenvironment, different from peritumoral immune hotspots, warranting further study in the context of immunotherapies. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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