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Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti–PD-1 Therapy
Abstract Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study, we found that melanoma patients exhibited a distinct gut mycobiota structure compared with healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, whereas Saccharomyces cerevisiae and Debaryomyces hansenii were less abundant. During anti–PD-1 treatment, the relative amount of Malassezia restricta and C. albicans increased. A higher level of Saccharomyces paradoxus was associated with a positive response to anti–PD-1 treatment, whereas a higher level of Tetrapisispora blattae was associated with a lack of clinical benefits. High levels of M. restricta and C. albicans, elevated serum lactate dehydrogenase, and being overweight were linked to increased risk of melanoma progression and poorer response to anti–PD-1 treatment. Thus, this study has revealed melanoma-associated mycobiome dysbiosis, characterized by altered fungal composition and fungi species associated with a higher risk of melanoma progression, identifying a role for the gut mycobiome in melanoma progression.
Exploring correlations between gut mycobiome and lymphocytes in melanoma patients undergoing anti-PD-1 therapy
Abstract Research has shown that the microbiome can influence how the immune system responds to melanoma cells, affecting the course of the disease and the outcome of the therapy. Here, we used the metagenomic approach and flow cytometry analyses of blood cells to discover correlations between gut fungi of metastatic melanoma patients enrolled in anti-PD-1 therapy and lymphocytes in their blood. We analyzed the patterns of associations before the first administration of anti-PD-1 therapy (BT, n = 61) and in the third month of the therapy (T3, n = 37), allowing us to track changes during treatment. To understand the possible impact of gut fungi on the efficacy of anti-PD-1 therapy, we analyzed the associations in clinical beneficiaries (CB, n = 37) and non-beneficiaries (NB, n = 24), as well as responders (R, n = 28) and non-responders (NR, n = 33). Patients with LDH < 338 units/L, overall survival (OS) > 12, CB, as well as R, had lower levels of Shannon diversity (p = 0.02, p = 0.05, p = 0.05, and p = 0.03, respectively). We found that the correlation pattern between intestinal fungi and lymphocytes was specific to the type of response, positive or negative. When comparing CB and NB groups, correlations with opposite directions were detected for C. albicans, suggesting a response-specific immune reaction. For CB, M. restricta exhibited a set of correlations with different types of lymphocytes, with prevalent positive correlations, suggesting a robust immune response in the CB group. This result extends our former research, where M. restricta and C. albicans were associated with an increased risk of melanoma progression and a poorer response to anti-PD-1 treatment.
Host Factors Associated with Gut Mycobiome Structure
The human gut is inhabited by many organisms, including bacteria and fungi, that may affect human health. However, research on human gut mycobiome is still rare.