European journal of cancer (Oxford, England : 1990) · 2025
Quantitative spatial profiling of PD-1/PD-L1 and TIGIT/CD155 interaction indicates poor survival outcome and resistance to adjuvant chemotherapy in pancreatic adenosquamous carcinoma.
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Chen Xianlong, Sun Shanyue, Li Shuofeng, Yu Shuangni, Chen Jie, Chen Xinyuan, Shi Xiaohua, Liang Zhiyong
Аннотация
BACKGROUND: Pancreatic adenosquamous carcinoma (PASC) is a rare, highly aggressive pancreatic cancer. Its therapeutic response varies, presumably due to tumor microenvironment (TME) complexity.
METHODS: We investigated whether using multiparameter algorithms to measure key immunosuppressive mechanisms in the TME could identify strong predictors of survival and response to adjuvant chemotherapy (ACT). Pre-treatment tumor tissues from 120 patients with PASC were stained using multiplexed quantitative immunofluorescence (training cohort: 92 patients; validation cohort: 28 patients). Novel Automated Quantitative Analysis (AQUA) algorithms were used for spatial profiling of biomarker-positive cells. Biomarker co-localization was determined in pathologist-selected tumor regions. The impact of certain biomarker signatures, including TIGIT/CD155 co-expression and PD-1/PD-L1 interaction scores, on survival outcomes and response to ACT was determined.
RESULTS: In the training cohort, PD-1/PD-L1 colocalization scores were significantly associated with advanced AJCC stage and perineural invasion. A TME with high PD-1/PD-L1 and TIGIT/CD155 co-localization scores represented a unique subtype, characterized by decreased cytotoxic T cell and increased suppressive immune checkpoint molecule levels. High PD-1/PD-L1 and TIGIT/CD155 co-localization scores were independent indicators of worse survival outcomes. Additionally, patients with low TIGIT/CD155 colocalization scores were more likely to benefit from ACT. These findings were reproducible in the external validation cohort.
CONCLUSIONS: Quantitative spatial profiling of the PD-1/PD-L1 and TIGIT/CD155 suppression pathways using novel AQUA algorithms could help predict patient outcomes and ACT responses reliably, guiding development of more effective personalized management for PASC.
METHODS: We investigated whether using multiparameter algorithms to measure key immunosuppressive mechanisms in the TME could identify strong predictors of survival and response to adjuvant chemotherapy (ACT). Pre-treatment tumor tissues from 120 patients with PASC were stained using multiplexed quantitative immunofluorescence (training cohort: 92 patients; validation cohort: 28 patients). Novel Automated Quantitative Analysis (AQUA) algorithms were used for spatial profiling of biomarker-positive cells. Biomarker co-localization was determined in pathologist-selected tumor regions. The impact of certain biomarker signatures, including TIGIT/CD155 co-expression and PD-1/PD-L1 interaction scores, on survival outcomes and response to ACT was determined.
RESULTS: In the training cohort, PD-1/PD-L1 colocalization scores were significantly associated with advanced AJCC stage and perineural invasion. A TME with high PD-1/PD-L1 and TIGIT/CD155 co-localization scores represented a unique subtype, characterized by decreased cytotoxic T cell and increased suppressive immune checkpoint molecule levels. High PD-1/PD-L1 and TIGIT/CD155 co-localization scores were independent indicators of worse survival outcomes. Additionally, patients with low TIGIT/CD155 colocalization scores were more likely to benefit from ACT. These findings were reproducible in the external validation cohort.
CONCLUSIONS: Quantitative spatial profiling of the PD-1/PD-L1 and TIGIT/CD155 suppression pathways using novel AQUA algorithms could help predict patient outcomes and ACT responses reliably, guiding development of more effective personalized management for PASC.