B cells and tertiary lymphoid structures promote immunotherapy response.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
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
Аннотация
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.