Stimulation of tumor infiltrating B-cells improves ex-vivo TIL expansion for melanoma sample immunotherapy I

Many studies have shown association of tumor infiltrating B-cells and presence of tertiary lymphoid structure with improved clinical responses to immune checkpoint inhibitors therapy. We hypothesized that their presence could also have an impact on TIL therapy response. To address this, we performed RNA-seq of FFPE samples from a cohort of patients that received TIL therapy. Melanoma tumors collected prior to TIL infusion were evaluated for immune content in 9 responders and 11 non-responders to TIL therapy. Our data demonstrate an increase in class-switched memory B-cells in responders compared with non-responders to TIL therapy. In the myeloid compartment, increased presence of dendritic cell populations (pDC, aDC, and iDC) and basophils was observed in responders to TIL therapy, as well as higher content of γδ T cells and effector memory CD8+ T cells (CD8+ Tem) in the T-cell compartment. Next, we assessed the TLS presence in the same cohort by a gene expression signature of 12 chemokines using principal component analysis. The responders showed a higher TLS score compared with the non-responder patients, suggesting that patients responding to TIL therapy had more TLS in their tumors than the non-responder patients. These observations indicate that, same as in the immune checkpoint inhibitors therapy response, presence of B-cells and TLS might have a positive impact in the clinical outcome to TIL therapy. RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) melanoma samples from patients enrolled in Moffitt Cancer Center’s TIL clinical trials. The data was analyzed acocordantly to the response to TIL therapy.