Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients

Clin Cancer Res. 2018 Dec 15;24(24):6345-6354. doi: 10.1158/1078-0432.CCR-18-1231. Epub 2018 Aug 28.


Purpose: Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment.

Experimental design: We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options.

Results: The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy.

Conclusions: Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor*
  • Biopsy
  • Cell Line, Tumor
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Disease Models, Animal
  • Drug Resistance, Neoplasm*
  • Drug Synergism
  • Gemcitabine
  • Gene Expression
  • Humans
  • Immunomodulation / drug effects*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Mesothelioma / diagnosis
  • Mesothelioma / drug therapy
  • Mesothelioma / immunology*
  • Mesothelioma / metabolism
  • Mesothelioma, Malignant
  • Mice
  • Positron Emission Tomography Computed Tomography
  • Prognosis
  • Treatment Outcome
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Deoxycytidine
  • Gemcitabine