Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma

Autor: Giorgio Gaglia, Megan L. Burger, Cecily C. Ritch, Danae Rammos, Yang Dai, Grace E. Crossland, Sara Z. Tavana, Simon Warchol, Alex M. Jaeger, Santiago Naranjo, Shannon Coy, Ajit J. Nirmal, Robert Krueger, Jia-Ren Lin, Hanspeter Pfister, Peter K Sorger, Tyler Jacks, Sandro Santagata
Rok vydání: 2023
Předmět:
Zdroj: Cancer Cell. 41:871-886.e10
ISSN: 1535-6108
Popis: Lymphocytes play a key role in immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. Here, we used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of tumor-bearing lung tissues from a Kras/p53 (KP) mouse model and human resections. Networks of directly interacting lymphocytes (‘lymphonets’) emerge as a distinctive feature of the anti-cancer immune response. Lymphonets nucleate from small T-cell clusters and incorporate B cells with increasing size. CXCR3-mediated trafficking modulates lymphonet size and number, but neoantigen expression directs intratumoral localization. Lymphonets preferentially harbor TCF1+/PD1+ progenitor CD8 T cells involved in responses to immune checkpoint blockade (ICB). Upon treatment of mice with ICB therapy or a neoantigen-targeted vaccine, lymphonets retain progenitor and gain cytotoxic CD8 T-cell populations, likely via progenitor differentiation. These data show that lymphonets create a spatial environment supportive of CD8 T-cell anti-tumor responses.
Databáze: OpenAIRE