Research Progresses in Immunological Checkpoint Inhibitors for Breast Cancer Immunotherapy

Zhang, Wenxiang; Kong, Xiangyi; Ai, Bolun; Wang, Zhongzhao; Wang, Xiangyu; Wang, Nianchang; Zheng, Shan; Fang, Yi; Wang, Jing

doi:10.3389/fonc.2021.582664

Cited by 15 publications

(14 citation statements)

References 136 publications

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“…( Zhao et al, 2019 ), CTLA-4 also mediates the inhibitory effect of Tregs cells. ( Zhang et al, 2021 ). Secondly, HER2 itself can trigger an anti-tumor immune response in tumors amplified by ERBB2.…”

Section: Discussionmentioning

confidence: 99%

RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

Shao

Wei

et al. 2022

Front. Genet.

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Purpose: This study aims to reveal the relationship between RNA N6-methyladenosine (m6A) regulators and tumor immune microenvironment (TME) in breast cancer, and to establish a risk model for predicting the occurrence and development of tumors.Patients and methods: In the present study, we respectively downloaded the transcriptome dataset of breast cancer from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database to analyze the mutation characteristics of m6A regulators and their expression profile in different clinicopathological groups. Then we used the weighted correlation network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO), and cox regression to construct a risk prediction model based on m6A-associated hub genes. In addition, Immune infiltration analysis and gene set enrichment analysis (GSEA) was used to evaluate the immune cell context and the enriched gene sets among the subgroups.Results: Compared with adjacent normal tissue, differentially expressed 24 m6A regulators were identified in breast cancer. According to the expression features of m6A regulators above, we established two subgroups of breast cancer, which were also surprisingly distinguished by the feature of the immune microenvironment. The Model based on modification patterns of m6A regulators could predict the patient’s T stage and evaluate their prognosis. Besides, the low m6aRiskscore group presents an immune-activated phenotype as well as a lower tumor mutation load, and its 5-years survival rate was 90.5%, while that of the high m6ariskscore group was only 74.1%. Finally, the cohort confirmed that age (p < 0.001) and m6aRiskscore (p < 0.001) are both risk factors for breast cancer in the multivariate regression.Conclusion: The m6A regulators play an important role in the regulation of breast tumor immune microenvironment and is helpful to provide guidance for clinical immunotherapy.

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Section: Discussionmentioning

confidence: 99%

RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

Shao

Wei

et al. 2022

Front. Genet.

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“…Extensive interest in cancer immunotherapy is reported according to the clinical importance of CTLA-4 and PD-1/PD-L1 in immune checkpoint therapies ( 48 ). The main immune checkpoints for breast cancer include CTLA-4, PD-1/PD-L1, lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin domain and mucin 3 (TIM-3), and other molecules ( 49 ). Clinical trials like SOLTI-1503 PROMETEO TRIAL ( 50 ), KEYNOTE-086 ( 51 ), NIMBUS ( 52 ), KEYNOTE-173 ( 53 ), and KEYNOTE-522 ( 54 ) showed that immunological checkpoint inhibitors have made significant progress in breast cancer immunotherapy, which is expected to become a new treatment for breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Zheng

et al. 2022

Front. Immunol.

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PurposeTo identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.MethodsFerroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan–Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase–PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.ResultsInternal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.ConclusionsThe FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.

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“…Extensive interest in cancer immunotherapy is reported according to the clinical importance of CTLA-4 and PD-1/PD-L1 [programmed death (PD) and programmed death-ligand (PD-L1)] in immune checkpoint therapies ( 43 ). The main immune checkpoints for BRCA include cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed death receptor 1/programmed cell death ligand 1 (PD-1/L1), lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin domain and mucin 3 (TIM-3), and other molecules ( 44 ). Clinical trials like SOLTI-1503 PROMETEO TRIAL ( 45 ), KEYNOTE-086 ( 46 ), NIMBUS ( 47 ), KEYNOTE-173 ( 48 ), KEYNOTE-522 ( 49 ), and KEYNOTE-355 ( 50 ) showed that ICIs have made significant progress in BRCA immunotherapy, which is expected to become a new treatment for BRCA.…”

Section: Discussionmentioning

confidence: 99%

Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer

Zheng

Zhou

et al. 2022

Front. Oncol.

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PurposeNecroptosis is a mode of programmed cell death that overcomes apoptotic resistance. We aimed to construct a steady necroptosis-related signature and identify subtypes for prognostic and immunotherapy sensitivity prediction.MethodsNecroptosis-related prognostic lncRNAs were selected by co-expression analysis, and were used to construct a linear stepwise regression model via univariate and multivariate Cox regression, along with least absolute shrinkage and selection operator (LASSO). Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to measure the gene expression levels of lncRNAs included in the model. Based on the riskScore calculated, we separated patients into high- and low-risk groups. Afterwards, we performed CIBERSORT and the single-sample gene set enrichment analysis (ssGSEA) method to explore immune infiltration status. Furthermore, we investigated the relationships between the signature and immune landscape, genomic integrity, clinical characteristics, drug sensitivity, and immunotherapy efficacy.ResultsWe constructed a robust necroptosis-related 22-lncRNA model, serving as an independent prognostic factor for breast cancer (BRCA). The low-risk group seemed to be the immune-activated type. Meanwhile, it showed that the higher the tumor mutation burden (TMB), the higher the riskScore. PD-L1-CTLA4 combined immunotherapy seemed to be a promising treatment strategy. Lastly, patients were assigned to 4 clusters to better discern the heterogeneity among patients.ConclusionsThe necroptosis-related lncRNA signature and molecular clusters indicated superior predictive performance in prognosis and the immune microenvironment, which may also provide guidance to drug regimens for immunotherapy and provide novel insights into precision medicine.

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Research Progresses in Immunological Checkpoint Inhibitors for Breast Cancer Immunotherapy

Cited by 15 publications

References 136 publications

RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

RNA N6-Methyladenosine Regulators Contribute to Tumor Immune Microenvironment and Have Clinical Prognostic Impact in Breast Cancer

Identification of Ferroptosis-Related Prognostic Signature and Subtypes Related to the Immune Microenvironment for Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer

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