Search

Introduction: Density of tertiary lymphoid structures and numbers of tumor-infiltrating CD8+ve T cells confer positive prognostic value in lung cancer. However, in the majority of lung cancer patients the anti-tumor immune responses are poor, underscoring the existence of immune escape mechanisms used by cancer cells. Immunoglobulin-like transcripts (ILTs) are a group of membrane inhibitory receptors which negatively regulate the functions of immune cells. ILT3 expression has been observed in gastric cancer cells and associated with cancer immune escape. Aims: To analyze ILT3 expression and its association with lung cancer tolerance. Methods: We evaluated cellular expression of ILT3, density of intratumoral lymphoid follicles and numbers of tumor-infiltrating CD8+ve cells, by immunohistochemistry on paraffin-embedded tissue specimens of 39 lung adenocarcinoma patients, TNM stage IA-IIIA, who underwent thoracotomy from 2009 to 2011. ILT3 expression was related to density of lymphoid follicles and CD8+ve T cells. Results: ILT3 expression was observed on the surface and cytoplasm of lung cancer cells of 46% of the patients. Patients with ILT3+ve cancer cells showed a significantly lower density of intratumoral lymphoid follicles, (median, range 17916, 0-109937 μm 2 / optical field) than those with ILT3-ve cancer cells (64005, 0-155585 μm 2 / optical field), p=0.018. There were no differences observed in CD8+ve T cytotoxic cells and Disease Specific Survival of the patients. Conclusions: We may have discovered a novel immune checkpoint in human lung adenocarcinoma, which could offer untapped opportunities for therapeutic intervention.

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.