e24148 Background: Probiotics are crucial in oncology for enhancing gut health, boosting immune response, potentially improving immunotherapy efficacy, and reducing side effects of cancer treatments. Research links a healthy gut microbiome with better immunotherapy outcomes, however, more studies in this area are required to validate this hypothesis. Methods: Oncological patients at Hospital Ángeles Puebla's Comprehensive Cancer Center undergoing immunotherapy were invited to participate and provided their consent to receive a daily probiotic and prebiotic mix (including Lactobacillus rhamnosus, Bifidobacterium longum, Pediococcus pentosaceus, and others) for three months. Their health was closely monitored, and quality of life assessed using the EORTC-QLQ-C30 questionnaire at the start, day 45, and day 90. A Kruskal-Wallis H-test was conducted to correlate the EORTC-QLQ-C30 scores with their diagnosis, clinical stage, presence of comorbidities, and use of ancillary treatments, as well as a Spearman's test to associate these scores with their age. Results: 22 patients were included. Average age was 64.5 years, with 77% being male and 23% female. 68.18% were in stage IV, 4.55% in stage III, 18.18% in stage II, and 9.09% in stage I. Comorbidities included: diabetes in 31.82%, hypertension in 40.91%, and other diseases in 22.73%. Treatment regimens involved 81.81% receiving Anti-PD-L1 and 18.18% receiving Anti-PD-1. Additionally, 40.91% were on corticosteroids and another 40.91% on proton pump inhibitors as ancillary treatments. Median follow-up was 3.13 months, during which 23% of the patients experienced adverse events. Of these, 9.09% were grade 4 according to the CTCAE v.5, and 13.63% were grade 1. Significant differences were found between patients with hepatocellular carcinoma versus renal carcinoma in the overall score on day 1 (KW: 4.47, p-value: 0.0344), with no differences in the rest of the scores. Significant differences were also identified between patients with advanced-stage versus early or locally advanced-stage cancer in terms of pain (KWS: 4.091, p-value: 0.043), dyspnea (KWS: 4.355, p-value: 0.037), loss of appetite (KWS: 4.091, p-value: 0.043), constipation (KWS: 3.971, p-value: 0.046), and diarrhea (KWS: 4.355, p-value: 0.037). A negative correlation was found between age and social functioning (Spearman: -0.73, p-value: 0.03), as well as with the presence of pain (Spearman: -0.73, p-value: 0.04). Conclusions: In this study, we observed a decrease in symptoms and an increase in functionality and overall quality of life scores among the patients. This suggests that patients undergoing active immunotherapy treatment may benefit from the use of probiotics and prebiotics as an ancillary treatment. However, further extended studies with larger populations are necessary to corroborate our findings.