Yan Leyfman, Co-Founder and Executive Director of MedNews Week, shared a post on LinkedIn, about a recent article by Rodrigo Paredes et al. published in Journal for ImmunoTherapy of Cancer:
“NSCLC and Immunotherapy Resistance: Unpacking the Tumor Microenvironment (TME)
Despite advances with immune checkpoint inhibitors (ICIs), many NSCLC patients show resistance—why?
Emerging culprits:
- KEAP1 ➝ Drives oxidative stress adaptation & immune exclusion via NRF2 activation
- SMARCA4 ➝ Impairs antigen presentation through chromatin remodeling defects
- PTEN ➝ Promotes tumor growth & immunosuppression via PI3K/AKT pathway dysregulation
These mutations:
- Create a non-inflamed, immune-resistant TME
- Are linked to poor ICI outcomes, regardless of PD-L1 or TMB
- Often co-occur with KRAS/STK11, worsening resistance
Takeaway: Understanding these alterations is key to unlocking new strategies in precision immunotherapy for NSCLC.
Title: Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role of KEAP1, SMARCA4, and PTEN mutations
Authors: Rodrigo Paredes, Roberto Borea, Francesco Drago, Alessandro Russo, Giovanni Nigita, Christian Rolfo
Read the Full Artice on Journal for ImmunoTherapy of Cancer
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