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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
Nature, 01/2020, Letnik: 577, Številka: 7791Journal Article
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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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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