Cancer‐testis antigens as biomarkers for Merkel cell carcinoma: Pitfalls and opportunities

Abstract

Background: The prognosis and treatment options for metastatic Merkel cell carcinoma (MCC) are poor. The immune-privileged status of cancer-testis (CT) antigens imparts tumor specificity, making them ideal candidates for targeted immunotherapy. We investigate the usefulness of the CT antigens SPA17 (sperm protein-17 [SP-17]), IGF2BP3 (insulin-like growth factor-II mRNA-binding protein 3 [IMP-3]), and transmembrane protein with epidermal growth factor (EGF)-like and two follistatin-like domains 1 (TMEFF1) as potential MCC biomarkers and evaluate their possible utility in immunotherapy and molecularly targeted image-guided treatment. Methods: The CT antigens SP-17, IMP-3, and TMEFF1 were selected using transcriptome profiling to identify CT antigens expressed in MCC tumors. Antibodies directed against these CT antigens were stained. Twelve normal skin tissue samples were used as a control. The average percentage of positive cells in each tumor was computed. Results: Twelve of 14 (86%) MCC cases showed crisp nuclear staining for SP-17, with 2.06% of cells staining positive. IMP-3 showed crisp, perinuclear staining in all 14 MCC cases, with 52.93% MCC cells staining positive. TMEFF1 showed perinuclear staining in all 14 MCC cases, with 96.51% of tumor cells staining positive.Conclusions: CT antigens were found to be expressed in both MCC and some control tissues. SP-17 was the most specific yet the least sensitive. IMP-3 and TMEFF1 were both sensitive but not specific. CT antigens may represent valuable treatment targets in MCC. K E Y W O R D Simmunohistochemistry, IMP-3, Merkel cell carcinoma, SP-17, TMEFF1

IGF2BP3 promotes cell metastasis and is associated with poor patient survival in nasopharyngeal carcinoma

“… 4 , 5 , 6 , 7 , 8 , 9 Moreover, IGF2BP3 was also implicated in the regulation of cancer stemness, metabolism and immunity. 10 , 11 , 12 , 13 Accumulating evidence indicates that IGF2BP3 plays a tumour‐promoting role in human cancers. In renal cell carcinoma, high IGF2BP3 protein levels detected in both plasma and tissue were independently correlated with poor overall prognosis.…”

Identification of new biomarkers in immune microenvironment of testicular germ cell tumour

“…There is evidence that SPA17 played a vital role in lymph node metastasis and might be a novel therapeutic target for breast cancer (Zhou et al., 2019). Moreover, SPA17 was also demonstrated to be a novel CTA in metastatic Merkel cell carcinoma, multiple myeloma as well as other haematologic malignancies (Dasgeb et al., 2019; Li et al., 2007; Lim et al., 2001). Dadabayev et al systematically summarised the evidence supporting the highly immunogenic nature of SPA17 and suggested the potential of SPA17 as tumour vaccines (Dadabayev et al., 2005).…”

Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer

“…However, this approach could also be adapted for autologous material from VP-MCC patients, who often maintain a higher MCPyV antigenic burden (54). Potency of these products targeting TAg VP-MCC could be further enhanced by including CD8 + T cells with alternative tumor specificities such as MAGE-A3, survivin, and SPA17 expressed by VP-MCC (55)(56)(57). Although MCPyV TAg cells minimally express the exhaustion markers PD-1 and TIM3 after production, co-administration with ICIs could potentially improve potency and persistence of the adoptively transferred cells.…”