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Publications

Journal Article Review Epublish

PubMed: 40270972 DOI: 10.3389/fimmu.2025.1536428

Gemcitabine: immunomodulatory or immunosuppressive role in the tumor microenvironment.

Front Immunol 16:1536428

Authors: Mahnaz Nemati, Chou-Yi Hsu, Deepak Nathiya, M Ravi Kumar, Enwa Felix Oghenemaro, Muthena Kariem, Parjinder Kaur, Deepak Bhanot, Ahmed Hjazi, Tayebeh Azam Saedi

Affiliations

  • Amir Oncology Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
  • Thunderbird School of Global Management, Arizona State University, Phoenix, AZ, United States.
  • Department of Pharmacy Practice, NIMS Institute of Pharmacy, NIMS University Rajasthan, Jaipur, India.
  • Department of Basic Science & Humanities, Raghu Engineering College, Visakhapatnam, India.
  • Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Delta State University, Abraka, Delta State, Nigeria.
  • Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq.
  • Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq.
  • Department of Medical Analysis, Medical Laboratory Technique College, The Islamic University of Babylon, Babylon, Iraq.
  • Chandigarh Pharmacy College, Chandigarh Group of Colleges-Jhanjeri, Mohali, Punjab, India.
  • Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, India.
  • Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.
  • Department of Genetics, Faculty of Science, Islamic Azad University, Tonekabon, Iran.

Abstract

Gemcitabine (GEM), a nucleoside analog chemotherapy agent, has been widely used in the treatment of various cancers. In recent years, there has been growing interest in understanding the immunomodulatory or immunosuppressive effects of GEM. The immunomodulatory roles of GEM could influence the anti-tumor immune responses via several mechanisms, such as modulation of antigen presentation, cytokine production, and immune cell population. Furthermore, there is evidence that GEM enhances the therapeutic efficacy of immunotherapies, including oncolytic viruses, immune checkpoint inhibitors, CAR T-cells, and therapeutic vaccines. On the other hand, accumulating evidence also proposed that GEM may act as an immunosuppressive agent within the tumor microenvironment, resulting in immune evasion of tumor cells and tumor growth. These paradoxical roles of GEM in modifying immune responses highlight the complexity of GEM interaction with immune cells and responses within the tumor microenvironment. This review aims to provide an overview of the immunomodulatory and immunosuppressive effects of GEM within the tumor microenvironment and how GEM affects the efficacy of cancer immunotherapy.

MeSH

Cells, Neoplasms, Immunotherapy, Immunity, Therapeutics, Tumor Microenvironment