Transcriptional Phenocopies of Deleterious KEAP1 Mutations Correlate with Survival Outcomes in Lung Cancer Treated with Immunotherapy

Scalera, S.; Ricciuti, B.; Marinelli, D.; Mazzotta, M.; Cipriani, L.; Bon, G.; Schiavoni, G.; Terrenato, I.; Di Federico, A.; Alessi, J. V.; Fanciulli, M.; Ciuffreda, L.; De Nicola, F.; Goeman, F.; Caravagna, G.; Santini, D.; De Maria, R.; Cappuzzo, F.; Ciliberto, G.; Jamal-Hanjani, M.; Awad, M. M.; Mcgranahan, N.; Maugeri-Saccà, M.

doi:10.1158/1078-0432.CCR-24-0626

Co-occurring mutations in KEAP1 and STK11/KRAS have emerged as determinants of survival outcomes in patients with non–small cell lung cancer (NSCLC) treated with immunotherapy. However, these mutational contexts identify a fraction of nonresponders to immune checkpoint inhibitors. We hypothesized that KEAP1 wild-type tumors recapitulate the transcriptional footprint of KEAP1 mutations and that this KEAPness phenotype can determine immune responsiveness with higher precision compared to mutation-based models.

Transcriptional Phenocopies of Deleterious KEAP1 Mutations Correlate with Survival Outcomes in Lung Cancer Treated with Immunotherapy / Scalera, S., Ricciuti, B., Marinelli, D., Mazzotta, M., Cipriani, L., Bon, G., Schiavoni, G., Terrenato, I., Di Federico, A., Alessi, J.V., Fanciulli, M., Ciuffreda, L., De Nicola, F., Goeman, F., Caravagna, G., Santini, D., De Maria, R., Cappuzzo, F., Ciliberto, G., Jamal-Hanjani, M., et al.. - In: CLINICAL CANCER RESEARCH. - ISSN 1078-0432. - 30:19(2024), pp. 4397-4411. [10.1158/1078-0432.CCR-24-0626]