Abstract 4488: Effector B cells and tertiary lymphoid structures predict response to immune checkpoint blockade in solid tumors

Background: Cytotoxic T cell markers, PD-L1, and mutational burden have been identified as biomarkers of response to immune checkpoint blockade (ICB). However, there is a growing appreciation of B cells as biomarkers and mediators of response. We recently conducted a phase II trial of neoadjuvant ICB (NCT02519322) in patients with resectable melanoma, and found increased B cell infiltration in responders (R) versus non-responders (NR). Methods: We further investigated our B cell findings through whole transcriptomic profiling in samples with high tumor purity and also targeted immune profiling with deconvolution algorithm MCP counter. Spatial organization of the B cells was assessed with singlet and multiplex immunohistochemistry (IHC). Additionally, B cell phenotype was queried through mass cytometry. B cell gene expression signatures were validated in a cohort of renal cell carcinoma (RCC) patients (NCT02210117), and B cell phenotype in a metastatic melanoma cohort, both treated with ICB. Results: Whole transcriptomic analysis of the neoadjuvant melanoma ICB cohort identified that the most differentially expressed genes by response in baseline (b/l) samples were related to B cells and antibody production (MZB1, JCHAIN, IGLL5, FCRL5, p Conclusion: Together, these data suggest that B cells, more specifically those with activated effector phenotypes, and TLS predict response to ICB and may also be contributing mechanistically to response. Citation Format: Sangeetha M. Reddy, Beth Helmink, Jianjun Gao, Shaojun Zhang, Keren Yizhak, Moshe Sade-Feldman, Rafet Basar, Jorge Blando, Guangchun Han, Vancheswaran Gopalakrishnan, Hao Zhao, Wenbin Liu, Hussein Tawbi, Rodabe Amaria, Michael Davies, Jeffrey Gershenwald, Elizabeth M. Burton, James Allison, Michael Tetzlaff, Katy Rezvani, Nir Hacohen, Padmanee Sharma, Linghua Wang, Jennifer Wargo. Effector B cells and tertiary lymphoid structures predict response to immune checkpoint blockade in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4488.