HHLA2 overexpression is a novel biomarker of malignant status and poor prognosis in gastric cancer

Li, Wei; Tang, Liang; Chang, Haiyan; Huo, Song; Li, Yan

doi:10.1007/s13577-019-00280-2

Cited by 32 publications

(48 citation statements)

References 22 publications

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“…To link HERVs and cancer or biomarker usage to specific locus, future research should focus on the identification of single HERV sites. Existential of serological HERV-K response Poor [41] Gastric cancer HHLA2 overexpression Poor [65] Bladder urothelial carcinoma HHLA2 overexpression Poor [66]…”

Section: Resultsmentioning

confidence: 99%

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<p>Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values</p>

Cao

Kang

Xiang

et al. 2020

OTT

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Human endogenous retroviruses (HERVs) form an important part of the human genome, commonly losing their coding ability and exhibiting only rare expression in healthy tissues to promote the stability of the genome. However, overexpression of HERVs has been observed in various malignant tumors, including clear cell renal cell carcinoma (ccRCC), and may be closely correlated with tumorigenesis and progression. HERVs may activate the interferon (IFN) signaling pathway by a viral mimicry process to enhance antitumor immune responses. There is increasing interest in the diagnostic and prognostic value of HERVs in cancers, and they may be candidate targets for tumor immunotherapy. The review will introduce the biological functions of HERVs in ccRCC and their clinical value, especially in regard to immunotherapy.

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Section: Resultsmentioning

confidence: 99%

“…64 The abnormal expression of HHLA2 has prognostic significance in gastric cancer and bladder urothelial carcinoma. 65,66 The increased expression of HHLA2 in ccRCC tissues results in a shorter overall survival indicating that HHLA2 may be a potential prognostic marker of ccRCC. 19…”

Section: Roles Of Hervs In Ccrcc Early Diagnosis and Prognosis Predicmentioning

confidence: 99%

<p>Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values</p>

Cao

Kang

Xiang

et al. 2020

OTT

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“…High expression of B7-H5 in tumor leads to a better prognosis of PDAC and glioma, but leads to a worse prognosis of lung cancer, osteosarcoma, breast cancer, OSCC, human ccRCC, ICC, BUC and CRC. There are contradictions between the two studies [29,30] on the expression characteristics of B7-H5 in gastric cancer tumor tissues and their relationship with tumor prognosis, and further research is needed. Based on current research, B7-H5 and CD28H do not bind to other known B7 receptors or ligands, respectively, and the CD28H/B7-H5 pathway is not present in rats and mice.…”

Section: Discussionmentioning

confidence: 97%

“…In a study on gastric cancer prognosis , it was found that B7‐H5 expression is increased in gastric cancer tissue specimens compared to normal gastric tissue specimens by analyzing of B7‐H5 expression data of gastric cancer tissue samples in the database. In addition, studies have found that high B7‐H5 expression in tumor tissue is associated with advanced clinical stage, deep tumor invasion, lymph node metastasis, distant metastasis and short OS.…”

Section: B7‐h5 Expression In Cancer and Relationship With Cancer Progmentioning

confidence: 99%

“…These results suggest that B7‐H5 is largely an inducer of antigen‐presenting cells (APCs) response to inflammation. B7‐H5 is also expressed on activated myeloid cells, and widely expressed in human cancer tissues , including pancreatic ductal adenocarcinoma (PDAC) , lung cancer , osteosarcoma , breast cancer , oral squamous cell carcinoma (OSCC) , human clear cell renal cell carcinoma (ccRCC), intrahepatic cholangiocarcinoma (ICC), bladder urothelial (ccRCC) , ICC , bladder urothelial carcinoma (BUC) , colorectal cancer (CRC) , glioma and gastric cancer .…”

Section: Introductionmentioning

confidence: 99%

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Phenotypical and potential functional characteristics of different immune cells expressing CD28H/B7-H5 and their relationship with cancer prognosis

Zhong

Lang

et al. 2020

Clinical and Experimental Immunology

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Summary CD28H and B7‐H5 have been identified as receptor–ligand pairs in the B7/CD28 family, and have co‐stimulatory activity in immune cells. Here, we have systematically reviewed the research reports concerning the CD28H/B7‐H5 pathway. It was found that CD28H is mainly expressed in T cells and natural killer (NK) cells with naive and poorly differentiated properties, and repeated antigen stimulation leads to permanent loss of CD28H. In tumors, CD28H is mainly expressed in tissue‐resident memory (TRM) lymphocyte T cells, which is associated with improved tumor prognosis. B7‐H5 is a ligand for CD28H and is widely expressed in tumor cells. B7‐H5 expression is closely related to the prognosis of the tumor. Studies have shown that high expression of B7‐H5 in tumor is related to a worse prognosis for lung cancer, osteosarcoma, oral squamous cell carcinoma (OSCC), breast carcinoma, human clear cell renal cell carcinoma (ccRCC), intrahepatic cholangiocarcinoma (ICC), bladder urothelial carcinoma (BUC) and colorectal cancer (CRC), but is associated with a better prognosis for pancreatic ductal adenocarcinoma (PDAC) and glioma. Controversial views exist in studies on gastric cancer prognosis.

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Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma

Li,

You,

Xue

et al. 2024

Cancer Immunol Immunother

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Background HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression in various cancer types. Nevertheless, the precise function and interaction with immune cells remain poorly understood, particularly in laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate the biological significance of HHLA2 within the tumor microenvironment of human LSCC tissues and delineate the clinical relevance and functional roles of HHLA2 in LSCC pathogenesis. Methods Through multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from LSCC patients ( n = 72), the analysis was executed to assess the expression levels of HHLA2, density and spatial patterns of CD68 + HLA-DR + CD163 − (M1 macrophages), CTLA-4 + CD4 + FoxP3 + (CTLA-4 + Treg cells), CTLA-4 + CD4 + FoxP3 − (CTLA-4 + Tcon cells), exhausted CD8 + T cells, and terminally exhausted CD8 + T cells in LSCC tissues. Survival analysis was conducted to evaluate the prognostic significance of HHLA2 and these immune checkpoints or immune cell populations, employing COX regression analysis to identify independent prognostic factors. Results Kaplan–Meier (K–M) survival curves revealed a significant association between HHLA2 expression and overall survival (OS) in LSCC. Elevated levels of HHLA2 were linked to reduced patient survival, indicating its potential as a prognostic marker (HR: 3.230, 95%CI 0.9205–11.34, P = 0.0067). Notably, increased infiltration of CD68 + cells (total macrophages), STING + CD68 + HLA-DR + CD163 − (STING + M1 macrophages), CTLA-4 + CD4 + FoxP3 + , CTLA-4 + CD4 + FoxP3 − , PD-1 + LAG-3 + CD8 + T cells, and PD-1 + LAG-3 + TIM-3 + CD8 + T cells strongly linked to poorer survival outcomes ( P < 0.05). A discernible trend was observed between the levels of these immune cell populations, STING ...

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HHLA2 overexpression is a novel biomarker of malignant status and poor prognosis in gastric cancer

Cited by 32 publications

References 22 publications

<p>Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values</p>

<p>Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values</p>

Phenotypical and potential functional characteristics of different immune cells expressing CD28H/B7-H5 and their relationship with cancer prognosis

Unlocking the potential of HHLA2: identifying functional immune infiltrating cells in the tumor microenvironment and predicting clinical outcomes in laryngeal squamous cell carcinoma

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