B cells and tertiary lymphoid structures promote immunotherapy response
Beth A Helmink
(1)
,
Sangeetha M Reddy
(1)
,
Jianjun Gao
(1)
,
Shaojun Zhang
(1)
,
Rafet Basar
(1)
,
Rohit Thakur
(1)
,
Keren Yizhak
(2)
,
Moshe Sade-Feldman
(2)
,
Jorge Blando
(1)
,
Guangchun Han
(1)
,
Vancheswaran Gopalakrishnan
(1)
,
Yuanxin Xi
(1)
,
Hao Zhao
(1)
,
Wenbin Liu
(1)
,
Valerie Lebleu
(1)
,
Sarah Warren
,
Hussein A Tawbi
(1)
,
Padmanee Sharma
(1)
,
Rodabe N Amaria
(1)
,
Sapna Patel
(1)
,
Michael E. Davies
(3)
,
Patrick Hwu
(1)
,
Jeffrey E Lee
(1)
,
Jeffrey E Gershenwald
(1)
,
Anthony Lucci
(1)
,
Reetakshi Arora
(1)
,
Scott Woodman
(1)
,
Emily Z Keung
(1)
,
Pierre-Olivier Gaudreau
(1)
,
Alexandre Reuben
(1)
,
Christine N Spencer
,
Alex Cogdill
(1)
,
Elizabeth M Burton
(1)
,
Lauren E Haydu
(1)
,
Alexander J Lazar
(1)
,
Roberta Zapassodi
(4)
,
Deborah A Ledesma
(1)
,
Sufey Ong
,
Michael Bailey
,
Fernanda Kugeratski
(1)
,
Courtney Hudgens
(1)
,
Disha Rao
(5)
,
Oscar Krijgsman
(5)
,
Elisa A Rozeman
(5)
,
Daniel Peeper
(5)
,
Christian U. Blank
(5)
,
Ton Schumacher
(5)
,
Lisa Butterfield
(6)
,
Raghu Kalluri
(1)
,
James Allison
(1)
,
Florent Petitprez
(7)
,
Wolf Herman Fridman
(7)
,
Nir Hacohen
(2)
,
Katayoun Rezvani
(1)
,
Michael T Tetzlaff
(1)
,
Kevin Mcbride
(1)
,
Linghua Wang
(1)
,
Jennifer Wargo
(1)
1
The University of Texas M.D. Anderson Cancer Center [Houston]
2 Massachusetts General Hospital [Boston]
3 School of Engineering [Edinburgh]
4 Memorial Sloane Kettering Cancer Center [New York]
5 NKI - Netherlands Cancer Institute
6 PITT - University of Pittsburgh
7 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
2 Massachusetts General Hospital [Boston]
3 School of Engineering [Edinburgh]
4 Memorial Sloane Kettering Cancer Center [New York]
5 NKI - Netherlands Cancer Institute
6 PITT - University of Pittsburgh
7 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers
Sarah Warren
- Function : Author
Padmanee Sharma
- Function : Author
- PersonId : 924523
Patrick Hwu
- Function : Author
- PersonId : 924486
Alexandre Reuben
- Function : Author
- PersonId : 799665
- ORCID : 0000-0003-4510-0382
Christine N Spencer
- Function : Author
Sufey Ong
- Function : Author
Michael Bailey
- Function : Author
Courtney Hudgens
- Function : Author
- PersonId : 799666
- ORCID : 0000-0001-8312-7485
James Allison
- Function : Author
- PersonId : 924457
Jennifer Wargo
- Function : Author
- PersonId : 799667
- ORCID : 0000-0003-3438-7576
Abstract
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.
Origin | Files produced by the author(s) |
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