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Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
09:04

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Host Determinants of Immune Checkpoint Inhibitor Efficacy: Immune, Genetic, Metabolic, and Lifestyle Factors

Ali Awada1, Nicole Charbel1, Sary Faraj1

  • 1Division of Hematology and Oncology, Department of Internal Medicine, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon.

International Journal of Molecular Sciences
|May 27, 2026
PubMed

Insights

Host factors significantly influence cancer immunotherapy effectiveness, impacting patient responses to immune checkpoint inhibitors (ICIs). Understanding these determinants is key to personalizing cancer treatment strategies.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but show variable patient responses.
  • Tumor-intrinsic factors like PD-L1 expression and tumor mutational burden partially explain response variability.
  • Host-related factors are increasingly recognized as critical modulators of ICI efficacy.

Purpose of the Study:

  • To provide a comprehensive review of host factors influencing ICI efficacy.
  • To explore how diverse host determinants impact antitumor immune responses.
  • To highlight the potential for integrating host factors in personalized immunotherapy.

Main Methods:

  • Literature review of host determinants affecting ICI treatment.
  • Analysis of immune competence, T-cell repertoire, and cytokine profiles.
  • Examination of genetic, epigenetic, microbiome, metabolic, and lifestyle influences.

Main Results:

  • Host factors such as immune competence, T-cell diversity, and cytokine profiles play a significant role.
  • Germline genetics, HLA genotype, and epigenetic regulation impact immune responses to ICIs.
  • Gut microbiome, metabolic status, obesity, nutrition, lifestyle, co-medications, and comorbidities also affect treatment outcomes.

Conclusions:

  • Host-related factors are crucial for understanding and predicting ICI response variability.
  • Integrating diverse host determinants can improve patient stratification for immunotherapy.
  • Personalized immunotherapy strategies can be developed by considering individual host profiles.
Keywords:
concomitant medicationshost determinantshost geneticsimmune checkpoint inhibitorslifestyle factorsmetabolismmicrobiomepredictive biomarkerstreatment response

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