- Helmink, Beth A;
- Reddy, Sangeetha M;
- Gao, Jianjun;
- Zhang, Shaojun;
- Basar, Rafet;
- Thakur, Rohit;
- Yizhak, Keren;
- Sade-Feldman, Moshe;
- Blando, Jorge;
- Han, Guangchun;
- Gopalakrishnan, Vancheswaran;
- Xi, Yuanxin;
- Zhao, Hao;
- Amaria, Rodabe N;
- Tawbi, Hussein A;
- Cogdill, Alex P;
- Liu, Wenbin;
- LeBleu, Valerie S;
- Kugeratski, Fernanda G;
- Patel, Sapna;
- Davies, Michael A;
- Hwu, Patrick;
- Lee, Jeffrey E;
- Gershenwald, Jeffrey E;
- Lucci, Anthony;
- Arora, Reetakshi;
- Woodman, Scott;
- Keung, Emily Z;
- Gaudreau, Pierre-Olivier;
- Reuben, Alexandre;
- Spencer, Christine N;
- Burton, Elizabeth M;
- Haydu, Lauren E;
- Lazar, Alexander J;
- Zapassodi, Roberta;
- Hudgens, Courtney W;
- Ledesma, Deborah A;
- Ong, SuFey;
- Bailey, Michael;
- Warren, Sarah;
- Rao, Disha;
- Krijgsman, Oscar;
- Rozeman, Elisa A;
- Peeper, Daniel;
- Blank, Christian U;
- Schumacher, Ton N;
- Butterfield, Lisa H;
- Zelazowska, Monika A;
- McBride, Kevin M;
- Kalluri, Raghu;
- Allison, James;
- Petitprez, Florent;
- Fridman, Wolf Herman;
- Sautès-Fridman, Catherine;
- Hacohen, Nir;
- Rezvani, Katayoun;
- Sharma, Padmanee;
- Tetzlaff, Michael T;
- Wang, Linghua;
- Wargo, Jennifer A
Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1-10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11-15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.