Impact of Dietary Fiber Intake on the Immunological Response to Immunotherapy in Cancer Patients: A Scoping Review

ABSTRACT

Introduction

Immunotherapy has emerged as a major therapeutic strategy for cancer, and accumulating evidence indicates that the gut microbiota influences its effectiveness, highlighting the potential role of dietary fiber.

Objective

To evaluate the scientific evidence regarding the relationship between dietary fiber intake, immune modulation, and the response to immunotherapy in patients with cancer.

Methodology

An integrative review was conducted using the MEDLINE, BVS, and EMBASE databases with the descriptors “Neoplasms,” “Dietary Fiber,” and “Immunomodulation.” Original studies involving patients with cancer undergoing immunotherapy that evaluated dietary fiber intake through habitual diet, dietary intervention, or supplementation, as well as its association with immune response, gut microbiota, or clinical outcomes were included.

Results

A total of 325 records were identified, of which three studies met the inclusion criteria.

Discussion

Higher dietary fiber intake was associated with improved therapeutic responses and favorable changes in the gut microbiota. The included studies involved patients with melanoma receiving immune checkpoint inhibitors, predominantly anti‐PD‐1 therapy.

Conclusion

Dietary fiber plays a relevant role in gut microbiota modulation and may enhance the effectiveness of immunotherapy.

1. Introduction

Cancer remains one of the leading causes of morbidity and mortality worldwide, driving the continuous search for more effective therapeutic strategies. Among recent advances, immunotherapy has emerged as a major therapeutic approach by harnessing the patient's own immune system to combat tumor cells [1, 2].

Consequently, there is growing interest in understanding the factors that may influence therapeutic responses. Increasing evidence indicates that the gut microbiota plays a fundamental role in regulating the immune system, including its involvement in mechanisms of cancer control [3].

Diet plays a crucial role in modulating this ecosystem, particularly through dietary fiber intake. Dietary fibers serve as substrates for bacterial fermentation, leading to the production of short‐chain fatty acids (SCFAs), which exert well‐established immunomodulatory effects and promote an antitumor immune profile [4].

Despite recent advances, few reviews have comprehensively synthesized the available evidence regarding the relationship between dietary fiber intake, immune response modulation, and the effectiveness of immunotherapy in patients with cancer. Therefore, this review aims to evaluate the available scientific evidence linking dietary fiber intake to immune response modulation and the efficacy of immunotherapy in patients with cancer.

2. Methodology

2.1. Study Design

This scoping review was prospectively registered with the Open Science Framework (OSF) under DOI: 10.17605/OSF.IO/A58MZ. The review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses Extension for Scoping Reviews (PRISMA‐ScR) checklist, which was used as a reporting guideline rather than as a methodological framework for conducting the review.

2.2. Databases

The literature search was conducted in the following databases: MEDLINE (via PubMed), the Virtual Health Library (VHL), and Excerpta Medica Database (EMBASE) via Elsevier.

2.3. Descriptors and Search Strategy

The search strategy was developed using descriptors from the Health Sciences Descriptors (DeCS) and Medical Subject Headings (MeSH) databases: Neoplasms, Dietary Fiber, and Immunomodulation, combined using the Boolean operators AND and OR. The complete search strategy is provided in the Supporting Information.

2.4. Eligibility Criteria

Studies were included if they: involved human participants with cancer undergoing immunotherapy (any modality described by the authors, including immune checkpoint inhibitors, immunomodulatory targeted therapies, among others); evaluated dietary fiber intake (through habitual diet, dietary intervention, or supplementation); and assessed its association with immune response (e.g., biomarkers, immune modulation, or microbiota‐related responses) and/or clinical outcomes (e.g., treatment response, toxicity, survival, disease progression, or quality of life, when reported). Studies published up to June 2025 in English, Portuguese, or Spanish and available in full text were considered eligible.

The exclusion criteria comprised duplicate publications, literature reviews (including narrative, integrative, and systematic reviews, as well as meta‐analyses), editorials, letters to the editor, in vitro studies, and other publications that did not report original data from human participants or did not clearly address the relationship between dietary fiber and the response to immunotherapy in patients with cancer.

2.5. Screening

The screening process was conducted in accordance with the PRISMA recommendations. Titles and abstracts were independently screened by two reviewers, followed by full‐text assessment of potentially eligible studies. References were managed using Zotero for organization and duplicate identification and removal, whereas the screening process was performed using Rayyan. Disagreements between reviewers were resolved through consensus and, when necessary, by consultation with a third reviewer.

2.6. Data Extraction and Evidence Mapping

The included studies were organized in a spreadsheet, and the extracted data were systematized into a data synthesis matrix (Table 1). Data extraction was performed using a standardized approach focused on mapping the evidence relevant to the review objective, thereby enabling comparison and integrative analysis of the main findings.

TABLE 1.

General characteristics of the included studies.

Author	Objective	Study design	Sample/intervention	Assessment instrument	Immunotherapy	Main findings
Spencer et al. [5]	To analyze microbiota, fiber intake, and omega‐3 consumption in relation to immunotherapy response in melanoma	Prospective observational cohort study	128 patients with melanoma	NCI‐DSQ	Anti‐PD‐1	Fiber intake ≥ 20 g/day: clinical response of 82% vs. 59%; longer progression‐free survival; greater gut microbiota diversity.
Simpson et al.[6]	To evaluate the effect of a high‐fiber diet on the microbiota of patients undergoing immunotherapy	Prospective observational cohort study	103 patients with stage III melanoma	FFQ	Anti‐PD‐1 + Anti‐CTLA‐4	Microbiota enriched with Ruminococcaceae associated with better response and lower toxicity; increased production of SCFAs and B vitamins.
Farias et al.[7]	To investigate the impact of fiber and probiotics on microbiota and immunotherapy response	Randomized clinical trial	40 patients with advanced melanoma; intervention with up to 50 g/day of fiber	Dietary records + NCI‐DHQ	Anti‐PD‐1 ± CTLA‐4/LAG‐3	Preliminary data: increased microbial diversity, higher SCFA production, and activation of antitumor immune responses

Abbreviations: FFQ: Food Frequency Questionnaire; NCI‐DHQ: National Cancer Institute Dietary History Questionnaire; NCI‐DSQ: National Cancer Institute Dietary Screener Questionnaire.

2.7. Data Items (Variables) Extracted and Assumptions

The following variables were extracted from the included studies: author and year of publication, country, study design, population/sample characteristics (when available), cancer type, immunotherapy modality, method used to assess or define dietary fiber intake (habitual diet, dietary intervention, or supplementation, when reported), indicators of immune response (i.e., immune markers or findings reported by the authors), evaluated clinical outcomes, and the main results and conclusions.

For the purpose of evidence synthesis, the operational definitions of dietary fiber intake and immune response were accepted as reported by the authors of each included study, taking into account the expected heterogeneity inherent to scoping reviews.

3. Results

The initial search identified 325 records across the three databases. After the removal of 13 duplicates, 312 studies remained for title and abstract screening. Subsequently, 21 articles were selected for full‐text review, of which 18 were excluded for not meeting the eligibility criteria, resulting in three studies being included in this scoping review.

All included studies involved patients with melanoma receiving immune checkpoint inhibitors (ICIs), primarily anti‐PD‐1 monotherapy or anti‐PD‐1 combined with anti‐CTLA‐4 therapy. No studies involving other cancer types, pediatric populations, hematologic malignancies, or other immunotherapy modalities were identified, highlighting important gaps in the current body of literature.

Regarding the extent and nature of the available evidence, the included studies were limited in terms of study design (two prospective observational cohort studies and one ongoing randomized clinical trial), geographic representation, and the dietary assessment instruments employed, precluding direct comparisons of dietary fiber intake thresholds across studies. Furthermore, the available evidence was restricted to a single tumor type and one class of immunotherapeutic agents (immune checkpoint inhibitors), indicating that the relationship between dietary fiber intake and the response to immunotherapy in other malignancies (e.g., lung cancer, renal cell carcinoma, and urothelial carcinoma) and with other immunotherapeutic modalities (e.g., CAR‐T cell therapy and cancer vaccines) remains largely unexplored. These findings underscore the need for future scoping and systematic reviews, as well as additional primary studies, encompassing cancer types beyond melanoma. The characteristics of the included studies are presented in Table 1.

Dietary assessment methods varied across the included studies. Spencer et al. [5] used the National Cancer Institute Dietary Screener Questionnaire (NCI‐DSQ) to estimate habitual dietary fiber intake, classifying patients into groups with adequate (≥ 20 g/day) or inadequate (< 20 g/day) fiber intake. Simpson et al. [6] used a Food Frequency Questionnaire (FFQ), whereas Farias et al. [7] combined detailed dietary records with the NCI‐DSQ.

Overall, the included studies indicate that higher dietary fiber intake, particularly from whole foods, is associated with favorable modulation of the gut microbiota and improved responses to immunotherapy in patients with melanoma. These effects appear to be mediated primarily by increased microbial diversity, a greater abundance of bacteria belonging to the Ruminococcaceae family, enhanced production of short‐chain fatty acids (SCFAs), particularly butyrate, and activation of immune mechanisms associated with antitumor responses, supporting the relationship between diet, the gut microbiota, and the efficacy of immunotherapy.

4. Discussion

All included studies demonstrated an association between higher dietary fiber intake and greater microbial diversity, with implications for both tumor response and immune homeostasis. Spencer et al. [5] reported that patients consuming ≥ 20 g of dietary fiber per day exhibited greater gut microbial diversity, higher clinical response rates, and longer progression‐free survival.

Simpson et al. [6] found that dietary patterns characterized by higher fiber intake and a gut microbiota enriched with bacteria from the Ruminococcaceae family were associated with more favorable clinical responses, reduced systemic inflammation, and lower rates of immune‐related toxicity.

The clinical trial conducted by Farias et al. [7] evaluated the effects of a high‐fiber diet (up to 50 g/day), derived exclusively from whole foods, on the gut microbiota and immune responses in patients receiving immunotherapy. Although the findings are preliminary, they support the hypothesis that dietary modulation influences immune parameters and gut microbiota dynamics, resulting in beneficial effects such as increased microbial diversity, enhanced SCFA production, and activation of mechanisms associated with antitumor responses.

The findings of this review are consistent with those of previous studies. Zhang et al. [8] demonstrated that short‐chain fatty acids (SCFAs), particularly butyrate, play a key role in T‐cell activation and modulation of the tumor microenvironment, thereby creating conditions that are more favorable for responses to immunotherapy. Ting et al. [9] further demonstrated that the gut microbiota directly influences immune system regulation and modulates the mechanisms through which immunotherapies exert their effects, potentially affecting both treatment efficacy and toxicity. Likewise, Singh et al. [10] showed that butyrate contributes to immune homeostasis by promoting an anti‐inflammatory profile and enhancing the activity of CD8⁺ T cells, which are essential for tumor control.

5. Conclusion

The findings synthesized in this review reinforce the important role of dietary fiber intake in modulating the gut microbiota and enhancing the effectiveness of immunotherapy. The included studies suggest that a fiber‐rich diet is associated with a more diverse and balanced gut microbiota, which may promote improved immune responses while contributing to reduced immune‐related toxicity.

Despite these promising findings, it is important to acknowledge that the current evidence base has important limitations. To date, all available studies have focused exclusively on patients with melanoma within similar clinical settings. Furthermore, additional clinical trials are needed to evaluate specific nutritional interventions in the context of immunotherapy. It should also be noted that the individual patient cohorts included in the three studies were relatively small (ranging from 40 to 128 participants), and even when pooled (n = 271), the overall sample size remains insufficient to reliably exclude the potential confounding effects of factors such as obesity, physical activity, overall lifestyle, and broader dietary patterns on the observed associations between dietary fiber intake and the response to immunotherapy.

Author Contributions

Thales Allyrio Araújo Medeiros de Fernandes: conceptualization, investigation, funding acquisition, writing – original draft, writing – review and editing, visualization, validation, methodology, formal analysis, data curation. Roque Ribeiro da Silva Júnior: conceptualization, investigation, funding acquisition, writing – original draft, writing – review and editing, methodology, formal analysis, data curation. Micássio Fernandes de Andrade: conceptualization, investigation, funding acquisition, writing – original draft, writing – review and editing, visualization, validation, methodology, formal analysis, data curation. Valéria Duarte de Almeida: conceptualization, investigation, funding acquisition, writing – original draft, methodology, validation, visualization, writing – review and editing, data curation. Michele Edmila Silva Sousa: conceptualization, investigation, funding acquisition, writing – original draft, methodology, visualization, writing – review and editing.

Funding

This study was funded by the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil.

Ethics Statement

The authors have nothing to report.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Data S1: PRISMA‐ScR‐Fillable‐Checklist.

Data S2: Search Strategy.

Data Availability Statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.