Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses

Cui, Can; Wang, Jiawei; Fagerberg, Eric; Chen, Ping-Min; Connolly, Kelli A.; Damo, Martina; Cheung, Julie F.; Mao, Tianyang; Askari, Adnan S.; Chen, Shuting; Fitzgerald, Brittany; Foster, Gena G.; Eisenbarth, Stephanie C.; Zhao, Hongyu; Craft, Joseph; Joshi, Nikhil S.

doi:10.1016/j.cell.2021.11.007

Cited by 247 publications

(227 citation statements)

References 164 publications

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“…Then, we further analyzed the correlations between the infiltration proportions of immune cell and patients' survival in LUAD and found that a high infiltration of T follicular helper cell (p = 0.02) and eosinophil (p = 0.014) had significantly better prognosis compared to the low infiltration groups (Figure S3). The latest research supported our conclusion about the correlations of T follicular helper cell and patients' survival, in which neoantigen-driven CD4 T follicular helper cell and B cell collaboration promoted antitumor immunity by enhancing CD8 T cell effector functions (26).…”

Section: Construction Of a Prognostic Model Based On The Ferroptosis ...supporting

confidence: 67%

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Song

Wang

et al. 2022

Front. Oncol.

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Lung adenocarcinoma (LUAD) is the most diagnosed subtype of lung cancer; ferroptosis is widely involved in the pathological cell death associated with various cancers, including lung cancer. However, the comprehensive relationship between ferroptosis and LUAD is little known in molecular levels until now. In the present study, 513 LUAD patients could be aggregated into three clusters by consensus clustering based on RNA sequencing data of 291 ferroptosis-related genes (FRGs) in The Cancer Genome Atlas (TCGA) database; cluster2 had significant survival advantage compared to the other two clusters. A novel prognostic model of 8 differential FRGs was constructed to effectively divide LUAD patients into high- or low-risk group according to the risk scores by the Cox and LASSO regression analyses. The overall survival of LUAD patients in the high-risk group was significantly worse in the TCGA and GEO cohorts. Moreover, patients with radiation therapy or high clinical stage had obviously higher risk scores. We validated the differential mRNA and protein expression of four FRGs in paired tumor and normal samples from our clinical cohort. Our study constructed a novel FRG signature to predict the prognosis of LUAD patients, which might provide a new prognostic tool and potential therapeutic targets for LUAD.

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Section: Construction Of a Prognostic Model Based On The Ferroptosis ...supporting

confidence: 67%

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma

Song

Wang

et al. 2022

Front. Oncol.

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“…In non-cancer context, these cells play an important role during germinal center (GC) formation and present a crucial source of cytokines essential for GC expansion and B cell isotype class switching. In human cancers, the presence of TLS and the enrichment of Tfh and B cells correlate with prolonged survival and favorable therapeutic response in melanoma ( n = 39; PFS p = 0.003) [ 121 ], breast ( n = 794; PFS p = 0.0036) [ 122 ] and lung cancers ( n = 478; OS p = 0.0013) [ 123 ]. Interestingly, a recent study in a mouse model has shown that tumor-specific Tfh-B cells interactions as well as IL-21 production result in antitumor immunity by enhancing granzyme B expression by tumor-infiltrating CD8 + T cells [ 123 ].…”

Section: Effector Cd4 + T Cell Subsets In Cancersmentioning

confidence: 99%

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy

Khelil

Godet

Abdeljaoued

et al. 2022

Cancers

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Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.

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“…Antibodies in turn can impact downstream immune responses, including antibody-dependent cellular cytotoxicity (ADCC) by NK cells, phagocytosis by macrophages (ADCP), and antigen presentation and T cell priming by dendritic cells (DCs) (1,2). B cells express MHC II to directly serve as antigenpresenting cells, triggering T cell activation, including that of T follicular helper cells (5)(6)(7). As such, B cells are the major component and initiator of tertiary lymphoid structures (TLSs), which are favorable prognostic markers for colorectal, lung, breast, and pancreatic cancers (2).…”

Section: B Cells Can Exert Antitumor Activitymentioning

confidence: 99%

“…Interactions between T cells and B cells are critical for efficient antitumor immunity (5). Not only are T cells involved in regulating the differentiation and maturation of germinal center B cells, but this interplay is bidirectional such that B cells are needed for the differentiation and functionality of follicular helper T (Tfh) cells.…”

Section: The Higg1-g396r Variant and Crcmentioning

confidence: 99%

“…Not only are T cells involved in regulating the differentiation and maturation of germinal center B cells, but this interplay is bidirectional such that B cells are needed for the differentiation and functionality of follicular helper T (Tfh) cells. Mice with B cell deficiency or immunized with tumor antigen lacking the BCR-specific epitope failed to generate Tfh cells, and subsequently did not develop effective antitumor immunity (5). Based on emerging data on the importance of B cells in antitumor immunity, development of monotherapy or combination therapy modulating B cells and/or BCR signaling could lead to effective cancer immunotherapies.…”

Section: The Higg1-g396r Variant and Crcmentioning

confidence: 99%

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