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

Zhang, Hanyun; AbdulJabbar, Khalid; Moore, David A; Akarca, Ayse; Enfield, Katey SS; Jamal-Hanjani, Mariam; Raza, Shan E Ahmed; ... Yuan, Yinyin; + view all (2023) Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma. Cancer Research , 83 (9) pp. 1410-1425. 10.1158/0008-5472.CAN-22-2589. Green open access

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Abstract

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.

Type: Article
Title: Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/0008-5472.CAN-22-2589
Publisher version: https://doi.org/10.1158/0008-5472.CAN-22-2589
Language: English
Additional information: ©2023 The Authors; Published by the American Association for Cancer Research This open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.
Keywords: Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Tertiary Lymphoid Structures, Prognosis, Carcinoma, Squamous Cell, Lung, Tumor Microenvironment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > CRUK Cancer Trials Centre
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
URI: https://discovery.ucl.ac.uk/id/eprint/10169874
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