B cells and tertiary lymphoid structures promote immunotherapy response

BA Helmink, SM Reddy, J Gao, S Zhang, R Basar… - Nature, 2020 - nature.com
BA Helmink, SM Reddy, J Gao, S Zhang, R Basar, R Thakur, K Yizhak, M Sade-Feldman
Nature, 2020nature.com
Abstract Treatment with immune checkpoint blockade (ICB) has revolutionized cancer
therapy. Until now, predictive biomarkers,,,,,,,,–and strategies to augment clinical response
have largely focused on the T cell compartment. However, other immune subsets may also
contribute to anti-tumour immunity,,,–, although these have been less well-studied in ICB
treatment. A previously conducted neoadjuvant ICB trial in patients with melanoma showed
via targeted expression profiling that B cell signatures were enriched in the tumours of …
Abstract
Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers, , , , , , , , – and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity, , , –, although these have been less well-studied in ICB treatment. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling 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-counter) 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.
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