Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies

Wang, Chenwei; Xiong, Chengjie; Hsu, Yung-Chun; Wang, Xiaoling; Chen, Lin

doi:10.21037/aob-20-27

Cited by 27 publications

(21 citation statements)

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“…For this purpose, we compared immune genes and tumor-infiltrating immune cells among different clusters, which serve as a powerful indicator to assess the tumor immune microenvironment. HLA is involved in antigen molecule delivery during cellular immunity and plays an essential role in the antitumor immune mechanism (Wang C. et al, 2020). We observed that the expression levels of the HLA family and MHC-I molecule genes were significantly higher in cluster 1 than in cluster 2.…”

Section: Discussionmentioning

confidence: 77%

“…Our results show that the genes of the HLA family are significantly differentially expressed in different clusters (Figure 6A). Human leukocyte antigen (HLA) is a major histocompatibility complex (MHC) expression product in humans, an antigen-presenting molecule, and regulates the immune response (Wang C. et al, 2020). In cluster 1, HLA-A, HLA-B, HLA-C, HLA-DRA, HLA-DRB1, HLA-E, and other genes were notably more highly expressed than in cluster 2, implying a robust immune response in cluster 1 patients and a deficiency of immune function in cluster 2.…”

Section: Immune Landscape In Coad Patientsmentioning

confidence: 99%

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N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

Zhang

Liu

Lü

2021

Front. Cell Dev. Biol.

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BackgroundColon adenocarcinoma (COAD) is the most common type of colon cancer. To date, however, the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in COAD are largely unknown.Materials and MethodsThe m6A-related lncRNAs were identified from The Cancer Genome Atlas (TCGA) data set. Univariate and multivariate Cox regression analyses were performed to explore the prognostic m6A-related lncRNAs. Consistent clustering analysis was performed to classify the COAD patients into different subgroups based on the expression of m6A-related lncRNAs. The potential biological functions as well as differences in the stemness index and tumor immune microenvironment between different subgroups were analyzed. The prognostic m6A-related lncRNAs were used to establish an m6A-related lncRNA risk model to predict prognosis and survival status.ResultsWe identified 31 m6A-associated lncRNAs with prognostic values from the TCGA data set. Based on the expression of prognostic m6A-associated lncRNAs, TCGA-COAD patients were classified into three clusters using consistent clustering analysis. There was a low correlation of tumor stemness between the three clusters but a significant correlation with the tumor immune microenvironment as well as the tumor mutational load. Thirty-one prognostic-related m6A-associated lncRNAs were used to construct a risk model, which was further determined by survival analysis, receiver operating characteristic (ROC) curve, and univariate and multifactor Cox analysis. The m6A-related risk model demonstrates good performance in predicting prognosis and survival status. The model-based high-risk group exhibited poorer overall survival (OS) compared with the low-risk group.ConclusionIn this study, we construct a risk model that consists of 31 m6A-related lncRNAs with independent prognostic values in COAD. Our study shows the critical roles of these 31 m6A-related lncRNAs in the tumor immune microenvironment, indicating the prospect of informing prognostic stratification and the development of immunotherapeutic strategies for COAD patients.

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Section: Discussionmentioning

confidence: 77%

Section: Immune Landscape In Coad Patientsmentioning

confidence: 99%

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

Zhang

Liu

Lü

2021

Front. Cell Dev. Biol.

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“…HLAs are cell-surface proteins encoded by a group of MHC genes and functions to present the cancer cells to immune cells. Many immunotherapies are HLA dependent such as TILs therapy and TCR-engineered T cells (TCR-Ts) therapy ( Wang et al ). We found that PRKCB, PRKCH, and PRKCQ levels were directly associated with HLAs scores in almost most cancers, especially for PRKCB, whose elevated expression moderately to strongly controlled the HLA level in 28 cancer types ( R ˃ 0.3) ( Figure 8A ).…”

Section: Resultsmentioning

confidence: 99%

Pan-Cancer Study on Protein Kinase C Family as a Potential Biomarker for the Tumors Immune Landscape and the Response to Immunotherapy

Abdelatty

Sun

et al. 2022

Front. Cell Dev. Biol.

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The protein kinase C (PKC) family has been described with its role in some cancers, either as a promoter or suppressor. PKC signaling also regulates a molecular switch between transactivation and transrepression activity of the peroxisome proliferator-activated receptor alpha (PPARalpha). However, the role of different PKC enzymes in tumor immunity remains poorly defined. This study aims to investigate the correlation between PKC genes and tumor immunity, in addition to studying the probability of their use as predictive biomarkers for tumor immunity and immunotherapeutic response. The ssGSEA and the ESTIMATE methods were used to assess 28 tumor-infiltrating lymphocytes (TILs) and the immune component of each cancer, then correlated with PKC levels. Prediction of PKC levels-dependent immunotherapeutic response was based on human leukocytic antigen (HLA) gene enrichment scores and programmed cell death 1 ligand (PD-L1) expression. Univariate and multivariate Cox analysis was performed to evaluate the prognostic role of PKC genes in cancers. Methylation level and CNAs could drive the expression levels of some PKC members, especially PRKCI, whose CNGs are predicted to elevate their level in many cancer types. The most crucial finding in this study was that PKC isoenzymes are robust biomarkers for the tumor immune status, PRKCB, PRKCH, and PRKCQ as stimulators, while PRKCI and PRKCZ as inhibitors in most cancers. Also, PKC family gene levels can be used as predictors for the response to immunotherapies, especially HLAs dependent and PD-L1 blockade-dependent ones. In addition to its prognostic function, all PKC family enzymes are promising tumor immunity biomarkers and can help select suitable immune therapy in different cancers.

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“…Tumors with higher T cell trafficking have been shown to have a higher therapeutic response to immune therapy [ 120 ]. Malignant transformation is often associated with changes in HLA expression [ 121 , 122 , 123 ], and thus these defects in HLA expression and antigen presentation machinery can lead to decreased tumor cell recognition by cognate T cells. This can result in immune evasion by cancer cells and may have therapeutic implications with respect to response to CPIs [ 124 ].…”

Section: Potential Immune Evasion Mechanismsmentioning

confidence: 99%

Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer

Bansal

Reimers

Knoche

et al. 2021

Cancers

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Although most prostate cancers are localized, and the majority are curable, recurrences occur in approximately 35% of men. Among patients with prostate-specific antigen (PSA) recurrence and PSA doubling time (PSADT) less than 15 months after radical prostatectomy, prostate cancer accounted for approximately 90% of the deaths by 15 years after recurrence. An immunosuppressive tumor microenvironment (TME) and impaired cellular immunity are likely largely responsible for the limited utility of checkpoint inhibitors (CPIs) in advanced prostate cancer compared with other tumor types. Thus, for immunologically “cold” malignancies such as prostate cancer, clinical trial development has pivoted towards novel approaches to enhance immune responses. Numerous clinical trials are currently evaluating combination immunomodulatory strategies incorporating vaccine-based therapies, checkpoint inhibitors, and chimeric antigen receptor (CAR) T cells. Other trials evaluate the efficacy and safety of these immunomodulatory agents’ combinations with standard approaches such as androgen deprivation therapy (ADT), taxane-based chemotherapy, radiotherapy, and targeted therapies such as tyrosine kinase inhibitors (TKI) and poly ADP ribose polymerase (PARP) inhibitors. Here, we will review promising immunotherapies in development and ongoing trials for metastatic castration-resistant prostate cancer (mCRPC). These novel trials will build on past experiences and promise to usher a new era to treat patients with mCRPC.

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Human leukocyte antigen (HLA) and cancer immunotherapy: HLA-dependent and -independent adoptive immunotherapies

Cited by 27 publications

References 0 publications

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

N6-Methylandenosine-Related lncRNA Signature Is a Novel Biomarkers of Prognosis and Immune Response in Colon Adenocarcinoma Patients

Pan-Cancer Study on Protein Kinase C Family as a Potential Biomarker for the Tumors Immune Landscape and the Response to Immunotherapy

Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer

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