Background: The gut microbiome is a key determinant of response to cancer immunotherapy; however, current research has focused on a limited number of well-characterized commensal taxa. This narrow scope may overlook a broader range of microbial species that contribute to variability in tumor response, limiting a comprehensive understanding of microbiome-driven immunomodulation.
Hypothesis: We hypothesize that underexplored gut microbial taxa may influence tumor response through shared immunomodulatory functions similar to those observed in established immunotherapy-associated microbes.
Methods: A targeted narrative literature review was conducted using PubMed and additional scholarly databases, with article organization performed in Zotero. MeSH terms and microbiome–immunology–focused keywords were used to identify peer-reviewed studies describing immune-modulating effects of candidate gut microbial taxa. Representative organisms were selected to capture both established and underexplored contributors to host immune regulation, including Bacteroides thetaiotaomicron, segmented filamentous bacteria, Helicobacter spp., Lactobacillus plantarum, Clostridium butyricum, and Eubacterium limosum, as well as emerging candidates such as Oscillibacter spp. and Veillonella atypica. Studies were evaluated for evidence of immune interaction, including effects on innate and adaptive immune pathways, and for relevance to tumor biology and immunotherapy response. Studies were included if they (1) were peer-reviewed, (2) provided mechanistic, preclinical, or clinical evidence of microbiome–immune interaction, and (3) demonstrated relevance to tumor biology or immunotherapy response. Studies were excluded if they lacked immune-related outcomes, were non-peer-reviewed, duplicative, or not relevant to cancer or host immune modulation. Selected studies were qualitatively synthesized to evaluate shared immunomodulatory functions across taxa.
Results: Preliminary synthesis suggests that while certain taxa demonstrate well-established roles in modulating host immune responses, a broader group of underexplored microbes may exert similar functional effects on immune tone. Most available evidence is derived from preclinical and mechanistic studies, with limited direct evaluation in cancer-specific clinical contexts.
Conclusion: These findings support a shift toward a functional framework of microbiome–immune interaction and highlight underexplored microbial taxa as potential contributors to variability in cancer immunotherapy response. Further research is needed to validate these associations in clinical settings and to define their therapeutic potential.
Hypothesis: We hypothesize that underexplored gut microbial taxa may influence tumor response through shared immunomodulatory functions similar to those observed in established immunotherapy-associated microbes.
Methods: A targeted narrative literature review was conducted using PubMed and additional scholarly databases, with article organization performed in Zotero. MeSH terms and microbiome–immunology–focused keywords were used to identify peer-reviewed studies describing immune-modulating effects of candidate gut microbial taxa. Representative organisms were selected to capture both established and underexplored contributors to host immune regulation, including Bacteroides thetaiotaomicron, segmented filamentous bacteria, Helicobacter spp., Lactobacillus plantarum, Clostridium butyricum, and Eubacterium limosum, as well as emerging candidates such as Oscillibacter spp. and Veillonella atypica. Studies were evaluated for evidence of immune interaction, including effects on innate and adaptive immune pathways, and for relevance to tumor biology and immunotherapy response. Studies were included if they (1) were peer-reviewed, (2) provided mechanistic, preclinical, or clinical evidence of microbiome–immune interaction, and (3) demonstrated relevance to tumor biology or immunotherapy response. Studies were excluded if they lacked immune-related outcomes, were non-peer-reviewed, duplicative, or not relevant to cancer or host immune modulation. Selected studies were qualitatively synthesized to evaluate shared immunomodulatory functions across taxa.
Results: Preliminary synthesis suggests that while certain taxa demonstrate well-established roles in modulating host immune responses, a broader group of underexplored microbes may exert similar functional effects on immune tone. Most available evidence is derived from preclinical and mechanistic studies, with limited direct evaluation in cancer-specific clinical contexts.
Conclusion: These findings support a shift toward a functional framework of microbiome–immune interaction and highlight underexplored microbial taxa as potential contributors to variability in cancer immunotherapy response. Further research is needed to validate these associations in clinical settings and to define their therapeutic potential.