Spatial Positioning of Immune Hotspots Reflects the Interplay between B and T Cells in Lung Squamous Cell Carcinoma
- Author(s)
- Zhang, H; Abduljabbar, K; Moore, DA; Akarca, A; Enfield, KSS; Jamal-Hanjani, M; Raza, SEA; Veeriah, S; Salgado, R; McGranahan, N; Le Quesne, J; Swanton, C; Marafioti, T; Yuan, Y;
- Details
- Publication Year 2023,Volume 83,Issue #9,Page 1410-1425
- Journal Title
- Cancer Research
- Publication Type
- Research article
- 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. 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.
- Keywords
- Humans; *Carcinoma, Non-Small-Cell Lung/pathology; *Lung Neoplasms/pathology; *Tertiary Lymphoid Structures; Prognosis; *Carcinoma, Squamous Cell/pathology; Lung/pathology; Tumor Microenvironment
- Department(s)
- Laboratory Research
- PubMed ID
- 36853169
- Publisher's Version
- https://doi.org/10.1158/0008-5472.CAN-22-2589
- Open Access at Publisher's Site
https://doi.org/10.1158/0008-5472.CAN-22-2589- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-08-20 06:18:13
Last Modified: 2024-08-20 06:56:39