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Lung cancer and mainly non-small cell lung cancer (NSCLC) still remain a prevalent malignancy worldwide despite sustained screening approaches. Furthermore, a significant proportion of the cases are diagnosed at advanced stages when conservative therapy is often unsuccessful. Cell senescence is an endogenous antitumor weapon but when it is upregulated exerts opposite activities favoring tumor metastasizing and poor response to therapy. However, little is known about this dangerous relationship between cell senescence and NSCLC outcome or on potential approaches to mitigate its unfavorable consequences. We discuss cell senescence focusing on immune senescence, its cell and humoral effectors (namely immune senescence associated secretory phenotype-iSASP), its impact on NSCLC outcome, and its biomarkers. Senotherapeutics as mitigating approaches are also considered based on the availability of experimental data pertinent to NSCLC. Characterization of NSCLC subsets in which immune senescence is a risk factor for poor prognosis and poor therapeutic response might be very helpful in supporting the addition of senotherapeutics to conventional cancer therapy. This approach has the potential to improve disease outcome but more studies in this area are necessary.

Immune senescence in non-small cell lung cancer management: therapeutic relevance, biomarkers, and mitigating approaches