Targeting novel immune checkpoints in the B7-H family: advancing cancer immunotherapy from bench to bedsideLuo, Yuan, Liu
et alTrends Cancer (2025)
Abstract: The B7-H family of immune checkpoint molecules is a crucial component of the immune regulatory network for tumors, offering new opportunities to modulate the tumor microenvironment (TME). The B7-H family - which includes B7-H2 (inducible T cell costimulatory ligand, ICOSL), B7-H3, B7-H4, B7-H5 (V-domain immunoglobulin suppressor of T cell activation, VISTA), B7-H6, and B7-H7 (HHLA2) - is known for its diverse roles in regulating innate and adaptive immunity. These molecules can exhibit co-stimulatory or co-inhibitory effects on T cells, influencing processes such as T cell activation, differentiation, and effector functions, and they are involved in the recruitment and polarization of various immune cells. This review explores the structural characteristics, receptor-ligand interactions, and signaling pathways associated with each B7-H family member. We also discuss the family's impact on tumor immunity and potential therapeutic strategies.Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.
Immune marker expression and prognosis of early breast cancer expressing HER3Lee, Ryu, Nikas
et alEur J Cancer (2024) 213, 115081
Abstract: There is a strong rationale for targeting HER3, as HER3 contributes to tumorigenesis and treatment resistance. However, the prognostic role of HER3 and their association with immunoregulatory protein expression has not been established.The main objective of this study was to investigate the prognostic role of HER3 expression and identify immunoregulatory marker expression according to HER3 status. HER3 expression and 10 immunoregulatory protein (PD-1/PD-L1/PD-L2/IDO/TIM-3/OX40/OX40L/B7-H2/B7-H3/B7-H4) expression was identified in 320 stage I-III breast cancer patients who received curative surgery at Seoul National University Hospital in 2008. The median follow-up duration was 88.8 months. Criteria for HER3 IHC was adopted from HER2 IHC score and only those with 3 + was considered positive.Among 320 patients, 213 (67.2 %) had luminal A disease, 30 (9.5 %) had luminal B disease, 28 (8.8 %) had HER2-positive disease, and 46 (14.5 %) had triple negative disease. HER3 expression was shown in 153 patients (47.8 %). Tumors with HER3-expression had more immunogenic tumor microenvironment compared to HER3-negative tumor. In addition, patients with HER3 expression had favorable 5-year relapse free survival compared to HER3-negative patients (5-year RFS 92.5 % vs. 85.2 %, p = 0.038). However, in the multivariate analysis, HER3 expression was not a prognostic factor, but expression of immunoregulatory protein was a prognostic factor.This study identified immunoregulatory protein expression according to HER3 status in breast cancer patients. As tumor with HER3 expression have more immunogenic microenvironment, investigating combination treatment of HER3 targeting agent and immunotherapy in HER3 expressing breast cancer may be promising.Copyright © 2024. Published by Elsevier Ltd.
Chemotherapy resistance in acute myeloid leukemia is associated with decreased anti-tumor immune response through MHC molecule and B7 family membersGe, Yin, Sun
et alDiscov Oncol (2024) 15 (1), 221
Abstract: Acute myeloid leukemia (AML) remains challenging due to chemotherapeutic drug-resistance (CDR). Aberrant expression B7 family proteins are involved in tumors evasion. We wonder whether B7 family protein alteration in AML CDR further supports tumor escape. Here, we establish AML cytarabine-resistant cell line U937/Ara-C and report on the expression MHC molecule and B7 family member. HLA-ABC was highly expressed similarly on both cell lines. MIC (MHC class I chain related) A/B and B7-H6 was moderately expressed on the surface of U937 and decreased dramatically by U937/Ara-C. In contrast, enhanced expression of B7-H1 and B7-H7 by U937/Ara-C was observed. HLA-DR and other B7 family members including CD80, CD86, B7-DC, B7-H2, B7-H3, B7-H4, and B7-H5 were not detected by both cell lines. Compared co-cultured with U937, peripheral blood mononuclear cells showed a decreased cytotoxicity when incubated with U937/Ara-C, as indicated by decreased levels of granzyme B and perforin production, accompanied with less TNF-α and lactate dehydrogenase secretion. In conclusion, AML CDR further evades the anti-tumor immune response which may through MHC molecule and B7 family members.© 2024. The Author(s).
Lipid droplets-related Perilipin-3: potential immune checkpoint and oncogene in oral squamous cell carcinomaHe, Liu, Dong
et alCancer Immunol Immunother (2024) 73 (5), 78
Abstract: Lipid droplets (LDs) as major lipid storage organelles are recently reported to be innate immune hubs. Perilipin-3 (PLIN3) is indispensable for the formation and accumulation of LDs. Since cancer patients show dysregulated lipid metabolism, we aimed to elaborate the role of LDs-related PLIN3 in oral squamous cell carcinoma (OSCC).PLIN3 expression patterns (n = 87), its immune-related landscape (n = 74) and association with B7-H2 (n = 51) were assessed by immunohistochemistry and flow cytometry. Real-time PCR, Western blot, Oil Red O assay, immunofluorescence, migration assay, spheroid-forming assay and flow cytometry were performed for function analysis.Spotted LDs-like PLIN3 staining was dominantly enriched in tumor cells than other cell types. PLIN3high tumor showed high proliferation index with metastasis potential, accompanied with less CD3+CD8+ T cells in peripheral blood and in situ tissue, conferring immunosuppressive microenvironment and shorter postoperative survival. Consistently, PLIN3 knockdown in tumor cells not only reduced LD deposits and tumor migration, but benefited for CD8+ T cells activation in co-culture system with decreased B7-H2. An OSCC subpopulation harbored PLIN3highB7-H2high tumor showed more T cells exhaustion, rendering higher risk of cancer-related death (95% CI 1.285-6.851).LDs marker PLIN3 may be a novel immunotherapeutic target in OSCC.© 2024. The Author(s).
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