TY - JOUR
T1 - B cells and tertiary lymphoid structures promote immunotherapy response
AU - Helmink, Beth A.
AU - Reddy, Sangeetha M.
AU - Gao, Jianjun
AU - Zhang, Shaojun
AU - Basar, Rafet
AU - Thakur, Rohit
AU - Yizhak, Keren
AU - Sade-Feldman, Moshe
AU - Blando, Jorge
AU - Han, Guangchun
AU - Gopalakrishnan, Vancheswaran
AU - Xi, Yuanxin
AU - Zhao, Hao
AU - Amaria, Rodabe N.
AU - Tawbi, Hussein A.
AU - Cogdill, Alex P.
AU - Liu, Wenbin
AU - LeBleu, Valerie S.
AU - Kugeratski, Fernanda G.
AU - Patel, Sapna
AU - Davies, Michael A.
AU - Hwu, Patrick
AU - Lee, Jeffrey E.
AU - Gershenwald, Jeffrey E.
AU - Lucci, Anthony
AU - Arora, Reetakshi
AU - Woodman, Scott
AU - Keung, Emily Z.
AU - Gaudreau, Pierre Olivier
AU - Reuben, Alexandre
AU - Spencer, Christine N.
AU - Burton, Elizabeth M.
AU - Haydu, Lauren E.
AU - Lazar, Alexander J.
AU - Zapassodi, Roberta
AU - Hudgens, Courtney W.
AU - Ledesma, Deborah A.
AU - Ong, Su Fey
AU - Bailey, Michael
AU - Warren, Sarah
AU - Rao, Disha
AU - Krijgsman, Oscar
AU - Rozeman, Elisa A.
AU - Peeper, Daniel
AU - Blank, Christian U.
AU - Schumacher, Ton N.
AU - Butterfield, Lisa H.
AU - Zelazowska, Monika A.
AU - McBride, Kevin M.
AU - Kalluri, Raghu
AU - Allison, James
AU - Petitprez, Florent
AU - Fridman, Wolf Herman
AU - Sautès-Fridman, Catherine
AU - Hacohen, Nir
AU - Rezvani, Katayoun
AU - Sharma, Padmanee
AU - Tetzlaff, Michael T.
AU - Wang, Linghua
AU - Wargo, Jennifer A.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2020/1/23
Y1 - 2020/1/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85078126241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85078126241&partnerID=8YFLogxK
U2 - 10.1038/s41586-019-1922-8
DO - 10.1038/s41586-019-1922-8
M3 - Article
C2 - 31942075
AN - SCOPUS:85078126241
SN - 0028-0836
VL - 577
SP - 549
EP - 555
JO - Nature
JF - Nature
IS - 7791
ER -