CLSPN Is Expressed in Pancreatic Cancer and Can Be a Target for Immunotherapy.
Claspin (CLSPN), previously identified as a cisplatin-resistance driver and immunotherapy target in urothelial carcinoma, has not been characterized in pancreatic cancer, which remains poorly responsive to immune checkpoint blockade. This study aimed to determine whether CLSPN can be a target for immunotherapy in pancreatic cancer.
CLSPN expression and its prognostic association were analyzed using a TCGA pancreatic adenocarcinoma cohort. CLSPN induction by cisplatin (CDDP) and oxaliplatin (L-OHP) was assessed by western blotting and quantitative RT-PCR. The antigen-specific reactivity of previously established CLSPN-specific, HLA-A*02:01-restricted TCR-T cells (clone yc3) against the pancreatic cancer cell line PANC-1 was evaluated by IFN-γ ELISPOT assay, with and without platinum pretreatment.
High CLSPN expression was associated with shorter overall, disease-free, disease-specific, and progression-free survival. CLSPN protein and mRNA expression were detected in pancreatic cancer cell lines. The expression of CLSPN was increased by platinum exposure. yc3 TCR-T cells specifically recognized CLSPN peptide-pulsed T2 cells and produced IFN-γ upon coculture with HLA-A*02:01+/CLSPN+ PANC-1 cells, and their reactivity was increased by platinum treatment.
CLSPN is a platinum-inducible immunotherapy target in pancreatic cancer, and combining CLSPN-specific TCR-T cell therapy with platinum-based chemotherapy is a promising strategy for this disease.
CLSPN expression and its prognostic association were analyzed using a TCGA pancreatic adenocarcinoma cohort. CLSPN induction by cisplatin (CDDP) and oxaliplatin (L-OHP) was assessed by western blotting and quantitative RT-PCR. The antigen-specific reactivity of previously established CLSPN-specific, HLA-A*02:01-restricted TCR-T cells (clone yc3) against the pancreatic cancer cell line PANC-1 was evaluated by IFN-γ ELISPOT assay, with and without platinum pretreatment.
High CLSPN expression was associated with shorter overall, disease-free, disease-specific, and progression-free survival. CLSPN protein and mRNA expression were detected in pancreatic cancer cell lines. The expression of CLSPN was increased by platinum exposure. yc3 TCR-T cells specifically recognized CLSPN peptide-pulsed T2 cells and produced IFN-γ upon coculture with HLA-A*02:01+/CLSPN+ PANC-1 cells, and their reactivity was increased by platinum treatment.
CLSPN is a platinum-inducible immunotherapy target in pancreatic cancer, and combining CLSPN-specific TCR-T cell therapy with platinum-based chemotherapy is a promising strategy for this disease.
Authors
Miura Miura, Murata Murata, Murai Murai, Mizue Mizue, Hori Hori, Tange Tange, Sasaki Sasaki, Shijubou Shijubou, Kubo Kubo, Tsukahara Tsukahara, Kashiwagi Kashiwagi, Abe Abe, Idogawa Idogawa, Anazawa Anazawa, Hata Hata, Torigoe Torigoe, Morita Morita, Hirohashi Hirohashi
View on Pubmed