{
  "abstract": "Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, characterized by a profoundly immunosuppressive tumor microenvironment and resistance to immunotherapy. Obesity, a modifiable risk factor that increases PDAC incidence, exacerbates this immune evasion through metabolic inflammation and adipokine-driven signaling. Recent studies have implicated CXC chemokines, particularly CXCL5, as central mediators in shaping the immune landscape of PDAC. In a pivotal study, Walsh et al delineated a novel mechanism wherein adipocyte-derived cytokines (interleukin-1β and tumor necrosis factor) induce tumor-derived CXCL5 expression, thereby promoting myeloid-driven immunosuppression in obese PDAC models. Their findings demonstrated that CXCL5 ablation enhances CD8+ T-cell infiltration yet paradoxically increases monocytic myeloid-derived suppressor cell accumulation and arginase-1 expression, underscoring the complexity of chemokine signaling. Notably, only combinatorial targeting of CXCL5 and programmed cell death protein-1 yields therapeutic benefit, emphasizing the necessity of multiaxis interventions. This commentary synthesizes the mechanistic insights and translational implications of these findings, highlighting CXCL5 as a pivotal node linking metabolic dysfunction to immune resistance and a promising target for combinatorial immunotherapy in PDAC.",
  "authors": [
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou Key Laboratory of Digestive Diseases, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China"
      ],
      "name": "Liping Liang"
    },
    {
      "affiliations": [
        "Department of Gastroenterology and Hepatology, Guangzhou Key Laboratory of Digestive Diseases, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China"
      ],
      "name": "Yongjian Zhou"
    },
    {
      "affiliations": [
        "Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China"
      ],
      "name": "Le Liu"
    }
  ],
  "title": "Dual-faced CXCL5 holds the key to unlocking immunotherapy in obese pancreatic cancer",
  "uid": "a24e4ed9-4c7e-580f-b7b6-f9cd4aa7a9d3"
}