| First Author | Gaglia G | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 5 | Pages | 871-886.e10 |
| PubMed ID | 37059105 | Mgi Jnum | J:336846 |
| Mgi Id | MGI:7470587 | Doi | DOI:10.1016/j.ccell.2023.03.015 |
| Citation | Gaglia G, et al. (2023) Lymphocyte networks are dynamic cellular communities in the immunoregulatory landscape of lung adenocarcinoma. Cancer Cell |
| abstractText | 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. |
