• Gut microbiota in cancer immune response and immunotherapy — Abstract review
  • Aria Mohammadi,1,*
    1. Mycobacteriology and Pulmonary Research Department Pasteur Institute of Iran


  • Introduction: The gut microbiota is a systemic regulator of host immunity and a modifiable extrinsic factor that influences cancer development, immune‑evasion programs, and responses to immunotherapy. Microbial taxa and their metabolites (e.g., short‑chain fatty acids, secondary bile acids, polyamines) modulate dendritic cell function, T cell priming and polarization (Th1/Th17/Treg balance), myeloid suppressor recruitment, and NK cell activity, while barrier integrity and microbial translocation propagate gut‑derived signals to distant tumor microenvironments (TMEs). Integrating microbiome signatures with immune phenotypes (for example, TIGIT‑expressing NK/T cell populations) has emerged as a promising approach to predict and potentially improve immune checkpoint inhibitor (ICI) outcomes [1][2][3]. Objective: To synthesize findings from three key articles on (i) gut microbiota roles in cancer immunity and immunotherapy, (ii) TIGIT+ NK cells plus microbiome features as predictors of ICI response in melanoma, and (iii) the conceptual framing of immune evasion as a cancer hallmark, and to produce a unified, clinically relevant abstract review.
  • Methods: Scope and inputs Primary sources: (A) a narrative review on gut microbiota, cancer immune response, and immunotherapy; (B) a prospective clinical study linking TIGIT+ NK cells and gut microbiome features to ICI outcomes in melanoma; (C) the canonical framework describing immune evasion as a cancer hallmark [1][2][3]. Synthesis approach 1. Extraction: key mechanistic points, clinical associations, biomarkers, and intervention strategies were extracted from each source. 2. Thematic mapping: findings were grouped under mechanistic themes (antigen presentation, T cell/NK modulation, myeloid suppression, barrier and metabolite signaling), clinical evidence (associations, predictive models, intervention trials), and translational opportunities/limitations. 3. Integration: themes were reconciled against the immune‑evasion hallmark framework to position microbiome effects as tumor‑extrinsic contributors to immune escape and therapeutic susceptibility. 4. Presentation: results were condensed into a single integrated abstract review emphasizing clinically actionable conclusions and prioritized research steps. Limitations of the method This synthesis relied solely on the three supplied articles and their reported data and interpretations. It did not include an independent systematic literature search or meta‑analysis; where cohort heterogeneity or limited sample size were reported in the originals, those caveats were retained.
  • Results: Mechanistic and clinical data converge on a model in which gut microbes and metabolites shape innate and adaptive antitumor immunity by controlling antigen presentation, T cell and NK cell function, and immunosuppressive myeloid circuits. Cohort and interventional data indicate that microbiome composition correlates with ICI efficacy and toxicity; fecal microbiota transplant (FMT) or defined live biotherapeutics can transfer or restore sensitivity in models and early clinical studies. A prospective melanoma study demonstrated that combining baseline shotgun metagenomics (Barnesiella intestinihominis, Enterobacteriaceae) with peripheral TIGIT+ CD56high NK cell frequency produced a strong prediction of durable ICI benefit (AUC ≈ 0.85). These observations align with the broader concept that immune evasion is both tumor‑intrinsic and tumor‑extrinsic, with the microbiome acting as a manipulable modifier of the immune‑evasion landscape. Translation priorities include standardized multi‑omic profiling, mechanistic mapping of microbe-immune circuits, prospective trials of rational microbiome interventions (FMT, defined consortia, engineered microbes), and validation of integrated immune–microbiome biomarkers to guide personalized immunotherapy [1][2][3].
  • Conclusion: The gut microbiota constitutes an actionable extrinsic determinant of cancer immune surveillance and immunotherapy outcome. Mechanisms include modulation of dendritic cell maturation and antigen presentation, shaping of T cell and NK cell phenotypes (including checkpoints such as TIGIT), regulation of myeloid suppressor pathways, and systemic dissemination of microbial metabolites. Clinically, microbiome features—when combined with immune phenotyping—can improve baseline prediction of ICI benefit and reveal mechanistic targets (e.g., TIGIT) for combination strategies. Priority translational steps are: standardized, longitudinal multi‑omic profiling; mechanistic experiments linking specific microbes/metabolites to immune circuits in the TME; randomized trials of well‑characterized microbiome interventions integrated with ICI; and external validation of combined immune–microbiome biomarker panels. Addressing cohort variability, standardization of methods, safety of live‑microbe therapeutics, and the timing of antibiotics are essential to move microbiome‑precision oncology into routine practice [1][2][3].
  • Keywords: References 1. Zhou C‑B, Zhou Y‑L, Fang J‑Y. Gut microbiota in cancer immune response and immunothera