Favorable Immune Microenvironment in Patients with EGFR and MAPK Co-Mutations.

PURPOSE

Although -mutated patients generally do not benefit from checkpoint inhibitors (ICIs), some patients in the KEYNOTE-001 study consistently benefited from this treatment. This study investigated immune microenvironment characteristics to identify the subgroup of patients that may benefit from ICIs.

MATERIALS AND METHODS

Using data from The Cancer Genome Atlas Program (TCGA) and Cancer Proteome Atlas, TMB and protein level of PD-L1 were explored in the patients with mutations and wild-type patients. Different patterns of mutations (according to EGFR co-mutation with different downstream pathway genesets) were used to group mutation population. Estimated infiltration analyses were used to explore changes in the immune microenvironment.

RESULTS

This study analyzed somatic mutation data from 1287 patients from five cohorts (TCGA, Broad, The Tumour Sequencing Project, Memorial Sloan Kettering Cancer Center, Catalogue Of Somatic Mutations In Cancer database). The probability of mutation was approximately 14.30% (184/1287) and the co-mutation rate was 11.41% (21/184) in patients with mutations. Glycosaminoglycan-related pathways were significantly upregulated in the mutant group. -mutated patients had lower TMB and PD-L1 protein levels than those in wild-type patients. Increase immature DCs infiltration and decreased NK CD56dim, T gamma delta, cytotoxic, and Th2 cell infiltration were the main immune changes in -mutated patients. Patients with -MAPK co-mutations had higher levels of TMB and PD-L1 protein expression. Meanwhile, the co-mutated patients had a similar immune microenvironment as that in wild-type patients.

CONCLUSION

In this study, we defined a subgroup of patients with -MAPK co-mutations. These co-mutated patients may benefit from ICI treatment.