Spatial Heterogeneity of TMEs in cHL and PDAC: Mechanistic Insights and Therapeutic Perspectives

Abstract

The tumor microenvironment (TME) is an important niche for tumor progression and the development of therapeutic resistance. Spatial omics technologies enable researchers to study cellular ecology and interactions within the TME in situ, compensating for the lack of spatial information in bulk sequencing or single-cell sequencing. Two tumor types exhibit intriguing and comparable TME features: classical Hodgkin lymphoma (cHL), characterized by dense immune cell infiltration but functionally inefficient immune responses; and pancreatic ductal adenocarcinoma (PDAC), a typical “immune-cold” tumor. This review summarizes recent research progress in spatial omics studies of these two tumor types, focusing on how cellular heterogeneity, immune cell distribution, stromal architecture, and metabolic niches collectively shape tumor pathobiological characteristics. Finally, several novel adjuvant therapeutic strategies, including oncolytic viruses, local immune agonists, and innovative drug delivery systems, are explored to reshape the TME and enhance the efficacy of immunotherapy.