Cancer-Testis Antigens in Triple-Negative Breast Cancer: Role and Potential Utility in Clinical Practice

Abstract

Breast cancer cells commonly express tumour-associated antigens that can induce immune responses to eradicate the tumour. Triple-negative breast cancer (TNBC) is a form of breast cancer lacking the expression of hormone receptors and cerbB2 (HER2) and tends to be more aggressive and associated with poorer prognoses due to the limited treatment options. Characterisation of biomarkers or treatment targets is thus of great significance in revealing additional therapeutic options. Cancer-testis antigens (CTAs) are tumour-associated antigens that have garnered strong attention as potential clinical biomarkers in targeted immunotherapy due to their cancer-restricted expressions and robust immunogenicity. Previous clinical studies reported that CTAs correlated with negative hormonal status, advanced tumour behaviour and a poor prognosis in a variety of cancers. Various studies also demonstrated the oncogenic potential of CTAs in cell proliferation by inhibiting cell death and inducing metastasis. Multiple clinical trials are in progress to evaluate the role of CTAs as treatment targets in various cancers. CTAs hold great promise as potential treatment targets and biomarkers in cancer, and further research could be conducted on elucidating the mechanism of actions of CTAs in breast cancer or combination therapy with other immune modulators. In the current review, we summarise the current understandings of CTAs in TNBC, addressing the role and utility of CTAs in TNBC, as well as discussing the potential applications and advantage of incorporating CTAs in clinical practise.

Immunotherapy in breast cancer: an overview of current strategies and perspectives

“…These proteins are normally expressed in embryonic stem cells and testicular germ cells, minimally expressed in most other normal tissues but often expressed at high levels in many different tumors 60 . Several hundred CTAs have been identified, and many have served as targets in vaccination involving patients with TNBC 61 . Perhaps the most notable is cancer/testis antigen 1B (NY-ESO-1) 62 .…”

Multi-antigen-targeted T-cell therapy to treat patients with relapsed/refractory breast cancer

“…We analyzed T-cell responses to the antigens targeted by the infused line (NY-ESO-1, SSX2, MAGE-A4, Survivin, and PRAME) as well as against a range of other non-targeted BC-expressed antigens including MAGE-A1, -A2B, -A3, -C1, and WT1. 24 , 27 , 30 , 37 We reasoned that the detection of such cells might be indicative of an active antitumor effect mediated by the cells infused, producing in vivo antigen spreading, thereby enhancing the antitumor benefits of our therapy. As shown in Figure 2 , most patients who experienced disease progression exhibited either a decrease or a transient increase in tumor-specific T cells, which peaked within 8 weeks of infusion and subsequently declined.…”

“… 9 – 11 To address this issue and with the goal of developing an effective immunotherapy for BC, we developed a non-engineered T-cell product containing both CD4+ (helper) and CD8+ (cytotoxic) T cells with native TCR specificity for multiple TAAs. Our target antigens were chosen based on the frequency of expression in BC of all subtypes (PRAME: 27–97%; SSX family: 4–65%; MAGE-A4: 4–86%; NY-ESO-1: 8–64%; and Survivin: 26–96%) 16 – 28 , 30 , 37 and immunogenicity to T cells. 24 , 28 , 30 , 31 We hypothesized that the infusion of such multiTAA T cells would be safe and promote anti-BC activity, minimizing the risk for antigen-negative relapses.…”

“…From day 10 and weekly thereafter, responder T cells were restimulated with pepmix-pulsed DCs in the presence of IL-15 (5 ng/mL) or IL-2 (50-100 U/mL) until sufficient numbers were achieved for patient infusion and release testing. The resulting multiTAA T-cell lines were harvested at a median of 26 [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] days post-T-cell initiation.…”

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

“…NY-ESO-1 and XAGE-1B are one of the CTAs, which are a large family of tumor-associated antigens only in germ cells of the testis and placenta ( 12 , 13 ), and in various malignant tumors, such as melanoma ( 14 ), squamous cell carcinoma ( 15 ), non-small cell lung cancer ( 16 ), gastric cancer ( 17 ), hepatocellular carcinoma ( 18 ), breast cancer ( 19 ), ovarian cancer ( 20 ), bladder cancer ( 21 ), prostate cancer ( 22 ), multiple myeloma ( 23 ), synovial sarcoma ( 24 ), and Ewing’s sarcoma ( 25 ). CTAs can be divided into two groups, those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens) ( 13 ).…”