Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy

Ying, Honggang; Xu, Jian; Zhang, Xiaozhen; Liang, Tingbo; Bai, Xueli

doi:10.1016/j.ebiom.2022.103987

Cited by 16 publications

(10 citation statements)

References 74 publications

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“… 48 HHLA2 was thought to play a dual role in carcinogenesis: one for immunostimulation and another for immunosuppression. 49 We examined the transcription of HHLA2 in epithelial cell subtypes, as well as some immune checkpoints potentially expressed in tumor cells ( Fig. 3 j).…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Wang

Ren

et al. 2022

eBioMedicine

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Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Wang

Ren

et al. 2022

eBioMedicine

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“…Several monoclonal antibodies, including nivolumab and pembrolizumab, have been approved to treat CRC [ 15 ]. However, there is a large group of patients with clinically advanced CRC whose tumors are resistant to anti-PD-1/PDL1 therapy, especially the patients with microsatellite-stable (MSS) tumors or with low microsatellite instability (MSI-L) [ 16 ]. Thus, exploring new targets such as immune checkpoints may increase the efficacy of ICBT.…”

Section: Discussionmentioning

confidence: 99%

Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer

Kula

Dawidowicz

Mielcarska

et al. 2023

IJMS

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The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

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“…However, there were also reports that HHLA2 was highly expressed in KIRC and predicted a favorable survival outcome in KIRC [39,40], which was consistent with our research. According to the report, HHLA2 has a costimulatory receptor TMIGD2 (transmembrane and immunoglobulin domain containing 2) and a coinhibitory receptor KIR3DL3 (killer cell Ig-like receptor, three Ig domains, and long cytoplasmic tail), which endows it with both immunostimulant and immunosuppression functions in cancer development [41]. These opposing functions emphasized that the expression and distribution of HHLA2 and its receptor may determine the immune response in the tumor microenvironment, thereby influencing prognosis.…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Novel Immune Checkpoint-Related Model in Clear Cell Renal Cell Carcinoma

Fan

Sun

et al. 2022

Disease Markers

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Background. With the highest mortality and metastasis rate, kidney renal clear cell carcinoma (KIRC) is one of the most common urological malignant tumors and not sensitive to chemotherapy and radiotherapy. Immunotherapy, which proves to be effective and a big progression, such as PD-1/PD-L1 inhibitors, is not sensitive to all KIRC patients. To predict prognosis and immunotherapy response, a novel immune checkpoint gene- (ICG-) related model is essential in clinics. Methods. From the public database-downloaded dataset, a novel ICG-related model for predicting prognosis and immunotherapy response in KIRC patients was built up and verified with R packages and Cox regression analysis. The Kaplan-Meier curve was plotted. Results. 39 ICGs were identified to have different expression in KIRC patients and enriched in immune-related biological pathways and activities. Three ICGs (CTLA4, TNFSF14, and HHLA2) were screened to generate KIRC-ICG model. The KIRC-ICG model was verified to be effective. With conducting KIRC-SYS model, KIRC-ICGscore was verified to be an independent factor regardless of age, gender, stage, grade, and TNM stage. Compared to the ICG-low subgroup, the ICG-high subgroup had more immune activities. KIRC-ICGscore was significantly positively correlated with the expression of Treg markers. KIRC-ICG model could also be reliable to predict immunotherapy response. Conclusion. The KIRC-ICG model was reliable to predict prognosis and immunotherapy response for KIRC patients and could be an independent factor regardless of clinical characteristics.

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Human endogenous retrovirus-H long terminal repeat-associating 2: The next immune checkpoint for antitumour therapy

Cited by 16 publications

References 74 publications

Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer

Overexpression and Role of HHLA2, a Novel Immune Checkpoint, in Colorectal Cancer

Construction and Validation of a Novel Immune Checkpoint-Related Model in Clear Cell Renal Cell Carcinoma

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