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The microbiome and diet in melanoma. The gut microbiome is now well-established as a determinant of immunotherapy response. Our group has been the first to demonstrate a role for diet in shaping the gut microbiome in melanoma patients and influencing immunotherapy outcomes, a finding that has now been validated by external groups. We have further shown that over-the-counter probiotic pills can negatively impact the gut microbiome and anti-tumor immunity. We have further demonstrated gut dysbiosis in melanoma patients compared to healthy volunteers, and in later-stage vs early-stage melanoma, suggesting a possible role for the microbiome in disease progression.

• Impact of a Prebiotic Food-enriched Diet (PreFED) in Combination With Ipilimumab/?Nivolumab Combination Immune Checkpoint Blockade (ICB) in ICB-refractory Melanoma Patients
• : Prebiotic Food-enriched Diet (PreFED) to Enhance the Microbiome and Response to First-line Immunotherapy in Unresectable Melanoma
• : Neoadjuvant Immune Checkpoint Blockade + a Prebiotic Food-enriched Dietary Intervention to Optimize Immune Response in Melanoma: NEO-PreFED

• Examining the microbiome as a mediator of fiber¡¯s effect on systemic and anti-tumor immunity in a fecal microbiota transplant (FMT) model

Identifying mechanisms of resistance is key to the rational development of more effective therapies or combinations. Our work in this area has identified predictors of resistance to both targeted and immune therapies, as well as cross-talk between oncogenic signaling, immune response, and cellular metabolism. This work includes the analysis of a Phase II trial of combined BRAF and MEK inhibition following failure of BRAF inhibitor monotherapy in which we showed that combination therapy was unable to overcome MAPK pathway reactivation in this setting. Our work in this area has identified predictors of resistance to both targeted and immune therapies, as well as cross-talk between oncogenic signaling, immune response, and cellular metabolism.

Mucosal melanoma is the rarest subtype of melanoma and has poor outcomes. We have previously collaborated on efforts to characterize clinical outcomes of mucosal melanoma. More recently, supported by a prior DOD award, we have been investigating the molecular drives of mucosal melanoma with abstracts presented at AACR, ASCO and the SITC Spring Scientific.

• Alliance A091903: A phase II trial of adjuvant Nivolumab with or without Cabozantinib 
• FP000014946: Delineating germline, tumor and extrinsic factors driving mucosal melanoma risk and response

As checkpoint inhibitor immunotherapy has become standard of care in metastatic melanoma, it is critical to assess the safety of these agents in populations which were not included in clinical trials as well as to better understand immunotoxicities (IOTOX). Dr. McQuade co-leads the MD Anderson IOTOX working group and collaborate with internal medicine colleagues as well as investigators around the world to characterize these toxicities and optimize treatment strategies for improved diagnosis and treatment.