Leveraging Evolutionary\nImmunology in Interleukin‑6\nand Interleukin-17 Signaling for Lung Cancer Therapeutics

Lung cancer is among the most common instances of cancer\nsubtypes\nand is associated with high mortality rates. Due to the availability\nof fewer therapies and delayed clinical investigations, the number\nof cancer incidences is rising dramatically. This is possibly an effect\nof immune modulations and chemotherapeutic drugs that raises cancer\nresistance. Among the list, IL-6 and IL-17 are host-derived paradoxical\neffectors that attune immune responses in malignant lung cells. Their\nexcessive release in the cytokine milieu stabilizes immunosuppressive\nphenotypes, resulting in cellular perturbations. During tumor development,\nthe significance of these molecules is reflected in their potential\nto regulate oncogenesis by initiating a myriad of signaling events\nthat influence tumor growth and the metastatic ability of benign cancer\ncells. Moreover, their transactivation contributes to antiapoptotic\nmechanisms and favors cancer cell survival via constitutive expression\nof immunoregulatory molecules. Co-evolution and gene duplication events\ncould be the major drivers behind cytokine evolution, which have prompted\ngeneric changes and, hence, the additive effect. The evolutionary\nmodel and statistical analysis provide evidence about the cytokines\nancestral relationships and site-specific conservation, which is more\nconvincing as both cytokines share cysteine-knot-like structures important\nin maintaining structural integrity. Funneling through the findings\ncould help find residues that serve a catalytic role in immune functioning.\nDesigning peptides or subunit vaccine formulations against those conserved\nresidues could aid in combating lung cancer pathogenesis.