Abstract
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.
Highlights
Cancer immunotherapy is emerging as a very promising strategy [1]
The best characterized pathways are the interactions between CTLA-4 and CD80/86, and the binding of PD-1 to PD-L1 to tumor cells [4–6]
CD244, B7-H4, BTLA, BTN2A1, BTN3A1, BTNL9, CD28, CD40, CD40LG, CD47, CD96, CD160, CD200, CEACAM1, DC-SIGN, LIGHT, SIRPA, PDL1, PDL2 and VISTA were down-regulated in breast cancer, whereas ADORA2A, B7-H3, CD70, CD80, CD86, CD137, CTLA-4, HVEM, IDO1, LAG-3, OX40, PD1 and TIGIT were up-regulated in breast cancer
Summary
Cancer immunotherapy includes active vaccination, adoptive cell transfer therapy and immune checkpoint blockade. Among these treatments, immune checkpoint blockade stands out as having remarkable clinical benefits for patients with melanoma, renal carcinoma, non-small-cell lung cancer and other solid tumors [2]. Tumor cells can hijack certain immune checkpoint pathways, escape immune surveillance and resist the cytotoxic effect of host T cells [1]. The best characterized pathways are the interactions between CTLA-4 and CD80/86, and the binding of PD-1 to PD-L1 to tumor cells [4–6]. Both pathways can inhibit the proliferation and function of T cells, causing immune evasion.
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