Social Factors Shape Gut Microbiome Without Affecting OS in Patients With Melanoma, Sarcoma Starting ICB

Higher social vulnerability was linked to an unfavorable gut microbiome but not worse overall survival (OS) in patients with melanoma or sarcoma receiving immune checkpoint blockade (ICB), with high dietary fiber intake emerging as a potentially modifiable mediator, according to a study published in Cancer.¹

Examining the Impact of Social Vulnerability and Dietary Fiber on the Gut Microbiome

The gut microbiome, influenced by diet and social determinants of health, is a key modulator of ICB response. In particular, dietary fiber supports beneficial gut bacteria linked to better ICB outcomes. Although individual social risk factors have been independently associated with both gut microbiome composition and clinical outcomes, the interplay of these factors remains unclear.

Building on prior findings that dietary fiber intake and the gut microbiome affect ICB response, the researchers hypothesized that social vulnerability may also play a role. Using the CDC’s Social Vulnerability Index (SVI), they examined the association between social determinants of health, dietary fiber intake, and gut microbial composition to identify potential targets that may individually or jointly influence response and survival in patients with melanoma and sarcoma initiating ICB.²

The study analyzed clinicopathologic data, baseline fiber intake, and gut microbiome profiles from 153 eligible patients.¹ Each patient’s SVI and fiber intake were evaluated for associations with microbiome composition, treatment response, and OS.

SVI values range from 0.00 to 1.00, with higher values indicating greater social vulnerability. The researchers used a cutoff value of 0.50 and stratified patients into high (≥ 0.50) and low (< 0.50) SVI groups. Similarly, dietary fiber intake was categorized using a median daily intake of 17.26 g, dividing patients into high (≥ 17.26 g) and low (< 17.26 g) intake groups.

Impact of Fiber Intake and Social Vulnerability on ICB Response and Survival

Of the 153 patients analyzed, 83.7% (n = 128) had melanoma and 16.3% (n = 25) had high-grade soft tissue sarcoma. All received either nivolumab monotherapy or combination therapy with ipilimumab, with 34.0% treated in the neoadjuvant setting and 66.0% in the noncurative intent setting.

Pathologic responses in the neoadjuvant setting did not differ significantly between disease types. However, clinical benefit varied, with partial responses more common in noncurative melanoma and stable disease more frequent in sarcoma and neoadjuvant melanoma.

Social vulnerability was moderate across cohorts and inversely correlated with dietary fiber intake (r = –0.18; P = .0398), indicating that patients with higher SVI consumed less fiber.

Whole genome sequencing of the gut microbiome showed that dietary fiber had a stronger association with beneficial bacterial composition than SVI. Higher fiber intake was linked to the enrichment of taxa such as Ruminococcaceae, whereas higher SVI was associated with reduced abundance of favorable bacteria like Bifidobacterium longum.

Higher dietary fiber intake was consistently associated with improved ICB outcomes and survival. Patients with high fiber intake experienced greater clinical benefit and pathologic response, and multivariable analysis confirmed a significant reduction in mortality risk (HR, 0.88; 95% CI, 0.80-0.97; P = .007). In contrast, SVI alone was not independently linked to survival.

Among patients in the neoadjuvant setting, high fiber intake mitigated the negative impact of elevated SVI on OS. In noncurative melanoma, high fiber intake was associated with clinically meaningful survival benefits regardless of SVI, underscoring dietary fiber as a potentially modifiable factor that may enhance ICB efficacy and outcomes, even for patients with higher social vulnerability.

Integrating Social and Environmental Context in ICB Research

The researchers concluded by acknowledging several limitations, including the study's retrospective single-institution design and modest sample size, which limit generalizability and causal inference. Still, they expressed confidence in their findings.

"Our findings reaffirm the need for social and environmental context in the evaluation of diet, microbiome composition, and clinical response in patients treated with ICB,” the authors wrote.

References

1. Fields BC, Traweek RS, Jiang K, et al. High dietary fiber is associated with improved outcomes in patients with melanoma and sarcoma treated with immunotherapy regardless of gut microbiome dysbiosis and social vulnerability. Cancer. 2026;132(6):e70335. doi:10.1002/cncr.70335
2. Social vulnerability index. CDC. July 22, 2024. Accessed March 19, 2026. https://www.atsdr.cdc.gov/place-health/php/svi/index.html