Deciphering the link between COPD and lung cancer: Cigarette smoke-induced immunosuppression at the crossroads between cancer immune surveillance and escape

Introduction: COPD increases the incidence of lung cancer independently of cigarette smoking. A hallmark of cancer is its remarkable ability to evade immunity. Cigarette smoke (CS) exposure has been associated with suppressed T cell immunity against pathogens. T cells are the frontline of defense against tumors. AIMS. To establish an orthotopic model of lung cancer in fully immunocompetent mice and investigate whether CS suppresses anti-tumor T cell responses. Methods: C57BL/6J wild type mice were either exposed to CS or sham. On day 30 syngeneic Lewis Lung Cancer (LLC) cells (or cancer-free media) were inoculated on the left lung lobe. On day 40 animals were sacrificed. Intratumoral and draining lymph node T cells were analyzed by 8-colour flow-cytometry. Results: A higher number of T helper and T cytotoxic (Tc) was observed in the lungs and draining lymph nodes of both CS-exposed and sham-exposed mice after inoculation of lung cancer cells compared to cancer free media, showing that cancer cell inoculation triggers adaptive immune responses in our mice models. However, intratumoral and lymph node T cells of CS-exposed mice with cancer showed a less activated/cytotoxic phenotype and produced higher levels of the inhibitory molecules TIM3, CTLA4, CD39, CD73 and of the immunosuppressive cytokine IL-10 than those of sham-exposed mice with cancer. Conclusions: Short-term CS-exposure suppresses early anti-tumor T cell responses in vivo. Impaired anti-cancer specific immunity in smokers could be a critical determinant of lung cancer escape from immunesurveillance mechanisms.