How Smoking-Induced Immune Reprogramming Drives the Speed and Progression of Lung Cancer Tumors and Treatment Considerations

Lung cancer is the most common and fatal malignant tumor, mostly driven by chronic inflammation in tobacco smoking. Although genetic mutations initiate tumorigenesis, the tumor microenvironment (TME), a recent discovery, is related to the development of lung cancer tumors and their progression. This literature review discusses how chronic inflammation, specifically smoking-induced inflammation, affects specific adaptive and innate immune responses. This process is known as immune cell reprogramming. Recent literature was analyzed to learn how these immune cells reprogram towards tumor-promoting phenotypes. Macrophages and T cells shift from anti-tumor roles to immunosuppressive, tumor-promoting states that accelerate progression and enable immune evasion. Cigarette smoke and nicotine drive macrophage polarization toward immunosuppressive M2 states and disrupt innate immune signaling. Simultaneously, T cells transition from protective antitumor effectors to dysfunctional, exhausted, or regulatory states that facilitate immune evasion. This literature review highlights immune cell reprogramming as an active driver of lung cancer progression rather than a secondary consequence of tumor growth. Ultimately, these findings suggest that further research is essential in order to close a critical knowledge gap regarding how immune dynamics influence the rate of tumor progression in order to improve patient outcomes.