Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q96BF3 (transmembrane and immunoglobulin domain containing 2)
 8 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune checkpoint blockade treatments bring remarkable clinical benefits to fighting several solid malignancies. However, the efficacy of immune checkpoint blockade in breast cancer remains controversial. Several clinical trials of immune checkpoint blockades focused on the effect of CTLA4 and PD1/PDL1 checkpoint inhibitors on breast cancer. Only a small portion of patients benefited from these therapies. Here we systematically investigated the expression of 50 immune checkpoint genes, including ADORA2A, LAG-3, TIM-3, PD1, PDL1, PDL2, CTLA-4, IDO1, B7-H3, B7-H4, CD244, BTLA, TIGIT, CD80, CD86, VISTA, CD28, ICOS, ICOSLG, HVEM, CD160, LIGHT, CD137, CD137L, OX40, CD70, CD27, CD40, CD40LG, LGALS9, GITRL, CEACAM1, CD47, SIRPA, DNAM1, CD155, 2B4, CD48, TMIGD2, HHLA2, BTN2A1, DC-SIGN, BTN2A2, BTN3A1, BTNL3, BTNL9, CD96, TDO, CD200 and CD200R, in different subtypes of breast cancer and assessed their prognostic value. The results showed that the expression patterns of these 50 immune checkpoint genes were distinct in breast cancer. High expression of B7-H3 mRNA was significantly associated with worse overall survival (OS), especially in patients with luminal A and luminal B breast cancer. The mRNA expression levels of TIM-3, ADORA2A, LAG3, CD86, CD80, PD1 and IDO1 had no relationship with OS in breast cancer. High expression levels of CTLA-4 and TIGIT were correlated with favorable prognosis in breast cancer. Interestingly, we observed that B7-H3 expression was negatively correlated with the efficacy of cyclophosphamide (CTX). In summary, our study suggested that B7-H3 has potential prognostic value in breast cancer and is a promising target for immune therapy.
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PMID:Prognostic value of immune checkpoint molecules in breast cancer. 3260 45

Blockade of the PD1 pathway is a broadly effective cancer therapy, but additional immune inhibitory pathways contribute to tumor immune evasion. HERV-H LTR-associating 2 (HHLA2; also known as B7H5 and B7H7) is a member of the B7 family of immunoregulatory ligands that mediates costimulatory effects through its interaction with the CD28 family member transmembrane and immunoglobulin domain containing 2 (TMIGD2). However, HHLA2 is also been known to have inhibitory effects on T cells. Here, we report that we have identified killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) as an inhibitory receptor for HHLA2 in T cells and natural killer (NK) cells and have generated HHLA2 and KIR3DL3 antibodies that block the immune-inhibitory activity of HHLA2, preserving the costimulatory signal. It is known that HHLA2 is frequently expressed in several tumor types, including clear cell renal cell carcinoma (ccRCC). We found that HHLA2 expression was non-overlapping with PDL1 expression in ccRCC, suggesting that HHLA2 mediates a mechanism of tumor immune evasion that is independent from PDL1. Blockade of both PD1 and KIR3DL3 pathways may be a more effective way to reverse tumor immune evasion.
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PMID:KIR3DL3 is an inhibitory receptor for HHLA2 that mediates an alternative immunoinhibitory pathway to PD1. 3322 11