Abstract
Lymphocytes are key for immune surveillance of tumors, but our understanding of the spatial organization and physical interactions that facilitate lymphocyte anti-cancer functions is limited. We used multiplexed imaging, quantitative spatial analysis, and machine learning to create high-definition maps of lung tumors from a Kras/Trp53-mutant mouse model and human resections. Networks of interacting lymphocytes (“lymphonets”) emerged as a distinctive feature of the anti-cancer immune response. Lymphonets nucleated from small T cell clusters and incorporated B cells with increasing size. CXCR3-mediated trafficking modulated lymphonet size and number, but T cell antigen expression directed intratumoral localization. Lymphonets preferentially harbored TCF1+ PD-1+ progenitor CD8+ T cells involved in responses to immune checkpoint blockade (ICB) therapy. Upon treatment of mice with ICB or an antigen-targeted vaccine, lymphonets retained progenitor and gained 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.
Original language | English (US) |
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Pages (from-to) | 871-886.e10 |
Journal | Cancer Cell |
Volume | 41 |
Issue number | 5 |
DOIs | |
State | Published - May 8 2023 |
Keywords
- CyCIF
- cancer vaccines
- computational biology
- immunotherapy
- lung adenocarcinoma
- multimodal data integration
- multiplexed imaging
- spatial biology
- spatial profiling
- systems biology
ASJC Scopus subject areas
- Oncology
- Cancer Research