B cell receptor signaling strength modulates cancer immunity

Ye, Jian; Lee, Peter P.

doi:10.1172/jci157665

Cited by 9 publications

(10 citation statements)

References 21 publications

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“…A combination of IFN‐α and anti‐PD‐1‐based immunotherapy resulted in enhanced antitumor activity in patients with unresectable HCC 25 . In addition, antigen contact with the BCR and subsequent signal transduction are the initial steps for B cell activation and proliferation, 26 and intertumoral B cells located in a tertiary lymphoid structure may contribute to the antitumor activity of immunotherapy 27 …”

Section: Discussionmentioning

confidence: 99%

The presence of vessels encapsulating tumor clusters is associated with an immunosuppressive tumor microenvironment in hepatocellular carcinoma

Zhang

Ono

Fujii

et al. 2022

Intl Journal of Cancer

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Recently, a distinct vascular pattern in hepatocellular carcinoma (HCC) called vessels encapsulating tumor‐forming clusters (VETC) has received attention because of its association with poor prognosis. However, little is known about the mechanism by which VETC promotes an aggressive phenotype at the molecular level. In our study, the association between differences in stepwise signal intensity in the HB phase and molecular subtypes and somatic mutations associated with the immune microenvironment were investigated using the International Cancer Genome Consortium (ICGC) cohort (66 patients). To our knowledge, this is the first study to analyze the molecular patterns of VETC using RNA‐Seq data. The VETC+ HCC group showed significantly lower overall survival and higher cumulative incidence of extrahepatic metastasis after curative hepatic resection than the VETC− HCC group. The VETC+ group exhibited molecular features indicative of lower immune activation than the VETC− group, suggesting that tumor cells in the VETC+ group were more likely to escape from the immune response, which could lead to the shorter OS (Overall survival) and higher risk of metastasis. On the other hand, gene expression levels of fibroblast growth factor receptors were upregulated in VETC+ HCC, suggesting that VETC+ HCC might benefit from lenvatinib treatment. Our results demonstrate that VETC+ HCC was associated with the suppression of tumor immune responses at the molecular level.

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Section: Discussionmentioning

confidence: 99%

The presence of vessels encapsulating tumor clusters is associated with an immunosuppressive tumor microenvironment in hepatocellular carcinoma

Zhang

Ono

Fujii

et al. 2022

Intl Journal of Cancer

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“…In tertiary lymphoid structures, B cells associate with T cells within tumors and activate CD4+ T cells to support the B cells in promoting anti-tumor immunity in a variety of ways [ 17 ]. In most cancer types, the infiltration of B cells is associated with a good prognosis; however, only some studies argue for a positive prognostic value of B cells [ 14 , 18 , 19 , 20 , 21 , 22 , 23 ]. For example, B cells are also reported to promote cancer proliferation by activating myeloid-derived suppressor cells, and the production of autoantibodies, tumor growth factors, and regulatory B cells, which directly and indirectly suppress Th1 and T cell responses [ 15 , 24 , 25 ].…”

Section: Antibody Diversity and Cancermentioning

confidence: 99%

Antibody Diversity in Cancer: Translational Implications and Beyond

et al. 2022

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Patients with cancer tend to develop antibodies to autologous proteins. This phenomenon has been observed across multiple cancer types, including bladder, lung, colon, prostate, and melanoma. These antibodies potentially arise due to induced inflammation or an increase in self-antigens. Studies focusing on antibody diversity are particularly attractive for their diagnostic value considering antibodies are present at an early diseased stage, serum samples are relatively easy to obtain, and the prevalence of antibodies is high even when the target antigen is minimally expressed. Conversely, the surveillance of serum proteins in cancer patients is relatively challenging because they often show variability in expression and are less abundant. Moreover, an antibody’s presence is also useful as it suggests the relative immunogenicity of a given antigen. For these reasons, profiling antibodies’ responses is actively considered to detect the spread of antigens following immunotherapy. The current review focuses on expanding the knowledge of antibodies and their diversity, and the impact of antibody diversity on cancer regression and progression.

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“…The detailed analysis process is showed in the flow chart. According to whether or not the BCR signaling pathway gene showed nonsynonymous mutation, the 47 patients in the Miao-LUAD cohort were divided into a BCR signaling MUT group (31) and a BCR signaling WT group (16). The results of the univariate Cox regression model showed that the BCR signaling pathway was a protective factor in the mutant group, which could predict better PFS and OS.…”

Section: Luad Patients With Bcr Signaling Pathway Mutation Have Bette...mentioning

confidence: 99%

“… 15 It is also reported that plasma cells differentiated from a B cell can infiltrate tumors and play an anti-tumor role by producing the tumor-specific antibody IgG1. 16 However, an overactivated BCR signaling pathway is also considered an important contributing factor in the occurrence and development of B-cell-derived malignant tumors such as chronic lymphocytic leukemia and diffuse large B-cell lymphoma. 17 , 18 Clinically, there are many inhibitors of BCR and related pathways, such as Bruton’s tyrosine kinas inhibition.…”

Section: Introductionmentioning

confidence: 99%

“…TP53 [25] TTN [22] MUC16 [17] KRAS [16] CSMD3 [14] COL11A1 [12] EGFR [12] LRP1B [12] MUC17 [12] OBSCN [11] RYR2 [11] ZFHX4 [11] CTNNA2 [10] FLG [10] KEAP1 [10] PAPPA2 [10] LPA [ 9] NF1 [ 9] PCLO [ 9] RELN [ 9] TP53 [25] TTN [22] MUC16 [17] KRAS [16] CSMD3 [14] COL11A1 [12] EGFR [12] LRP1B [12] MUC17 [12] OBSCN [11] RYR2 [11] ZFHX4 [11] CTNNA2 [10] FLG [10] KEAP1 [10] PAPPA2 [10] LPA [ 9] NF1 [ 9] PCLO [ 9] RELN […”

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confidence: 99%

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B Cell Receptor Signaling Pathway Mutation as Prognosis Predictor of Immune Checkpoint Inhibitors in Lung Adenocarcinoma by Bioinformatic Analysis

Lin¹,

Fang²,

Cheng³

et al. 2022

JIR

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Purpose The advent of immune checkpoint inhibitors (ICIs) is a revolutionary breakthrough. However, without the selection of a specific target population, the response rate of ICI therapy in lung adenocarcinoma (LUAD) is low, so a clinical challenge has arisen in effectively using biomarkers to determine which patients can benefit from ICI therapy. Methods In this study, patients were divided according to whether or not nonsynonymous mutations were present in the BCR signaling pathway, and univariate and multivariate Cox regression models were established based on a LUAD cohort treated with ICIs (Miao-LUAD). Then the relationship between the mutation status of the BCR signaling pathway and the prognosis of immunotherapy was examined. Finally, data from The Cancer Genome Atlas (TCGA) LUAD cohort, the Rizvi-LUAD, the Samstein-LUAD, and the Zhujiang Hospital of Southern Medical University LUAD (Local-LUAD) cohort were combined, and the mutation panorama, immunogenicity, tumor microenvironment (TME) and pathway enrichment analysis between the BCR signaling pathway mutant group (BCR signaling MUT) and the BCR signaling pathway wild group (BCR signaling WT) were comprehensively compared. Results It was found that, compared with the BCR signaling WT, the BCR signaling MUT had a significantly improved progression-free survival (PFS) rate and overall survival (OS) rate, higher immunogenicity (tumor mutational burden, neoantigen load, and DNA damage response signaling mutations), and anti-tumor immune microenvironment. Conclusion These results revealed that the mutation state of the BCR signaling pathway has potential as a biomarker to predict the efficacy of ICIs in LUAD.

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B cell receptor signaling strength modulates cancer immunity

Cited by 9 publications

References 21 publications

The presence of vessels encapsulating tumor clusters is associated with an immunosuppressive tumor microenvironment in hepatocellular carcinoma

The presence of vessels encapsulating tumor clusters is associated with an immunosuppressive tumor microenvironment in hepatocellular carcinoma

Antibody Diversity in Cancer: Translational Implications and Beyond

B Cell Receptor Signaling Pathway Mutation as Prognosis Predictor of Immune Checkpoint Inhibitors in Lung Adenocarcinoma by Bioinformatic Analysis

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