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Remodeling the pancreatic tumor microenvironment by chemotherapy: New opportunities for combination therapy

Yuemeng Tang1, Xiyuan Luo1, Feihan Zhou1

  • 1Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|May 10, 2026
PubMed

Insights

Pancreatic cancer (PDAC) has poor survival rates, and immunotherapy alone isn't effective. Combining chemotherapy with immunotherapy shows promise by altering the tumor microenvironment (TME) to improve treatment response.

Area of Science:

  • Oncology
  • Cancer Immunology
  • Translational Medicine

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) presents a significant clinical challenge with high mortality and low survival rates.
  • Immunotherapy has limited efficacy as a monotherapy for PDAC, necessitating alternative strategies.
  • Chemotherapy combined with immunotherapy demonstrates improved survival, suggesting chemotherapy modulates the tumor microenvironment (TME) to enhance immunotherapy efficacy.

Purpose of the Study:

  • To systematically review the immunosuppressive and stromal characteristics of the PDAC TME.
  • To delineate the effects of chemotherapy on TME remodeling.
  • To identify potential targets for combination therapies involving chemotherapy and immunotherapy.

Main Methods:

  • Systematic literature review.
  • Characterization of PDAC TME features.
  • Analysis of chemotherapy's impact on TME.
  • Identification of synergistic targets.

Main Results:

  • The PDAC TME is characterized by significant immunosuppressive and stromal components.
  • Chemotherapy can remodel the TME, potentially overcoming resistance to immunotherapy.
  • Specific TME features and chemotherapy-induced changes present opportunities for combination therapies.

Conclusions:

  • Understanding PDAC TME dynamics is crucial for improving treatment outcomes.
  • Chemotherapy-mediated TME modulation is a key factor in enhancing immunotherapy response.
  • Targeting specific pathways within the remodeled TME could lead to more effective therapeutic strategies for PDAC.
Keywords:
ChemotherapyImmunotherapyPancreatic cancerTumor microenvironment

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