Immunogenomics Demonstrate Predictive Capability to Immunotherapy Resistance in Uveal Melanoma
Source: OncLive, May 2024
Immunogenomic factors were found to be predictive of resistance to immunotherapy and to tumor susceptibility to the therapeutic class in patients with metastatic uveal melanoma, according to findings from a study published in Nature Communications.
Investigators profiled human uveal melanoma metastases (n = 100) using clinicogenomics, transcriptomics, and tumor-infiltrating lymphocyte (TIL) potency assessment, and discovered that 55% of metastases had tumor reactive TILs. To better harness the TILs, study authors developed the biomarker uveal melanoma immunogenomic score (UMIS). They showed that UMIS was strongly correlated with the percentage of tumor-reactive TIL cultures (rho?=?+0.47; P?=?7.06e?7), with reactive TIL cultures being rarely expanded among patients with a UMIS of less than 0.2.
Nineteen of the uveal melanoma metastases were used to manufacture TIL as part of a phase 2 clinical trial (NCT01814046). In this cohort, which included 6 responders, there was a strong correlation between source tumor UMIS and ex vivo anti-tumor reactivity of the post-rapid expansion of the TIL infusion product (n =?17; rho?=?+0.61; P?=?.011). UMIS was also strongly correlated with the magnitude of clinical tumor regression following adoptive transfer, including in patients who were refractory to immune checkpoint inhibitor therapy (n =?19; rho?=??0.68; P?=?.001).