MUC16 a promising biomarker of ICI response
medwireNews: Patients with solid tumors harboring MUC16 mutations may have better outcomes in response to immune checkpoint inhibitor (ICI) therapy than those carrying the wild-type gene, research suggests.
Tumors with MUC16 mutations also exhibited genomic factors associated with a good response to ICIs, including high tumor mutational burden (TMB) and PD-L1 expression, report Yuankai Shi and colleagues from the Chinese Academy of Medical Sciences & Peking Union Medical College in Beijing.
They therefore suggest that MUC16, which is “the third most frequently mutated gene in cancers,” could “serve as a prognostic factor to help optimize the application of ICI-based immunotherapy.”
The researchers evaluated the association between MUC16 status and ICI response in a cohort of 56 individuals with non-small-cell lung cancer (NSCLC) who received PD-1 or PD-L1 inhibitors and another cohort of 145 melanoma patients who received anti-CTLA-4 therapy.
MUC16 mutations were associated with significantly longer median overall survival with ICIs than wild-type MUC16 both in the NSCLC cohort, at unreached versus 11.3 months (hazard ratio [HR]=0.34), and the melanoma cohort, at 27.0 versus 9.7 months (HR=0.57).
And a significantly greater proportion of NSCLC patients harboring mutated MUC16 achieved complete or partial responses to ICIs, at 50% versus 19% of those with wild-type MUC16. The findings were similar in the melanoma cohort, with corresponding rates of 27% and 10%.
Shi et al also analyzed data pertaining to 10,195 participants of The Cancer Genome Atlas (TCGA) pan-cancer project, and found that MUC16 mutations, occurring in 19.68% of patients, appear “to be associated with reported genomic factors associated with response to and improved outcomes for ICI treatment in solid tumors.”
Specifically, the TMB was significantly higher among individuals with MUC16 mutations than among those with the wild-type gene, at a median of 230 and 48 mutations, respectively, and neoantigen load was significantly greater, at a median of 179 versus 48 neoantigens.
Furthermore, of the four different types of tumor immune microenvironment, the first type, “defined by positive CD8A and PD-L1 expression, [is] most likely [to] receive benefit from anti-PD1/PD-L1 therapies,” explain the authors, noting that this type was over-represented in MUC16-mutated versus wild-type tumors (43.8 vs 32.4%).
“These findings suggest that MUC16 mutation may be associated with superior response to ICIs in patients with solid tumors,” conclude Shi et al in JAMA Network Open.
Although this is “a further step toward the development of factors associated with outcomes for ICI therapy in solid tumors,” the investigators stress that “[a]dditional and larger clinical studies are required.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group