Prognostic value of immune checkpoint molecules in breast cancer

Jun Fang, Feng Chen, Dong Liu, Feiying Gu, Zhigang Chen, Yuezhen Wang, Jun Fang, Feng Chen, Dong Liu, Feiying Gu, Zhigang Chen, Yuezhen Wang

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.

Keywords: Breast cancer; Immune checkpoint molecules; Prognostic value.

Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

© 2020 The Author(s).

Figures

Figure 1. The heat map of immune…
Figure 1. The heat map of immune checkpoint genes in breast cancer and normal tissue
(A) The mRNA expression of 50 immune checkpoint genes in breast cancer and normal tissue. (B) The mRNA expression of 50 immune checkpoint genes in different subtype of breast cancer and normal tissue.
Figure 2. The correlation between inhibitory immune…
Figure 2. The correlation between inhibitory immune checkpoint genes mRNA expression and prognosis of breast cancer patients
(A,B) The B7-H3 (CD276) mRNA expression is associated with a worse OS (A) and RFS (B) in breast cancer patients. (C,D) The CTLA4 mRNA expression is associated with a better OS (C) and RFS (D) in breast cancer patients. (E,F) The TIGIT mRNA expression is associated with a better OS (E) and RFS (F) in breast cancer patients.
Figure 3. The correlation between B7-H3 mRNA…
Figure 3. The correlation between B7-H3 mRNA expression and prognosis of different subtypes of breast cancer patients
(A) The B7-H3(CD276) mRNA expression is associated with a worse OS in luminal A breast cancer patients; (B) the B7-H3 (CD276) mRNA expression is associated with a worse OS in luminal B breast cancer patients. (C,D) The B7-H3 (CD276) mRNA expression has no relationship with prognosis in basal breast cancer patients (C) and HER-2 amplification cases (D).
Figure 4. Association between inhibitory immune checkpoint…
Figure 4. Association between inhibitory immune checkpoint genes mRNA and sensitivity of different cell lines to target drugs
The regression figures of ADORA2A mRNA and efficacy of megestrol acetate (A), ADORA2A mRNA and efficacy of Tamoxifen (B), LAG-3 expression and efficacy of gemcitabine (C), LAG-3 expression and efficacy of Tamoxifen (D), CTLA-4 expression and efficacy of CTX (E), CTLA-4 expression and efficacy of everolimus (F), PD1 expression and efficacy of megestrol acetate (G), BT-H3 expression and efficacy of CTX (H). The data were transformed to Z-scores and were downloaded from Cell Miner Tools.

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