Detection of senescent cells in malignant ascites using mass cytometry and therapeutic strategies focused on cellular senescence

Abstract

Recent studies have revealed senescent non-malignant cells in the tumor microenvironment exhibit a secretory profi le under stress conditions; this senescence-associated secretory phenotype (SASP) promotes carcinogenesis and cancer progression. However, the role of senescent non-malignant cells in the metastatic process is not well-understood. We showed that fi broblast population shows p16 expression and SASP factors at high levels in the ascites of gastric cancer patients with peritoneal dissemination by single-cell mass cytometry (CyTOF). Moreover, we present the senolysis strategy in the tumor microenvironment based on the results of an in vivo validation. We identifi ed piperlongumine as the effective senolytic drug for senescent-fi broblasts. These fi ndings offer some notice toward a successful treatment targeting harmful senescent cells and provide the potential for clinical application for the future therapeutic strategy for combining conventional chemotherapy. progression. However, the role of senescent non-malignant cells in the metastatic process is not well-understood. We showed that fi broblast population shows p16 expression and SASP factors at high levels in the ascites of gastric cancer patients with peritoneal dissemination by single-cell mass cytometry (CyTOF). Moreover, we present the senolysis strategy in the tumor microenvironment based on the results of an in vivo validation. We identifi ed piperlongumine as the effective senolytic drug for senescent-fi broblasts. These fi ndings offer some notice toward a successful treatment targeting harmful senescent cells and provide the potential for clinical application for the future therapeutic strategy for combining conventional chemotherapy.