Abstract IA35: Immune contexture evolution during lung cancer carcinogenesis and its potential clinical implications

Abstract

Abstract Immune-checkpoint blockade has shown unprecedented durable clinical responses in patients with various cancer types, including lung cancer, which has created enormous interest among oncologists and immunologists to understand the interactions between cancer and host anticancer immunosurveillance. Tumors grow within an intricate network of epithelial cells, blood and lymphatic vessels, cytokines, and infiltrating immune cells. The location, density, and functional orientation of different immune cell populations constitute the tumor immune contexture that may profoundly impact clinical outcomes of cancer patients. Although most cancers have evaded host immunosurveillance at the time of presentation, an active anticancer immune response within tumor immune contexture, such as the presence of specific T-lymphocyte subsets, the absence of immunosuppressive elements, the localization and homogeneity of the immune infiltrate, specific features of its organization, and so on is often associated with a more favorable prognosis of cancer patients. There is a dynamic interaction between the host immune system and evolving cancer cells, a phenomenon termed immunoediting. Immunoediting is composed of three phases: elimination, equilibrium, and escape. The elimination phase refers to the phase when host immune responses are able to eradicate tumor cells of early carcinogenesis when the cancer cell molecular architectures are relatively simple. With selection and evolution, cancer cells become molecularly more complex and cancer immunoediting enters the next phase, equilibrium, during which tumor cells that have escaped elimination and have a nonimmunogenic phenotype are selected for growth. During this phase, new tumor cell variants emerge with various mutations that further increase overall resistance to immune attack. The last phase of immunoediting is the escape phase when tumor cell variants selected in the equilibrium phase have breached the host immune defenses, with various genetic and epigenetic changes conferring further resistance to immune detection. Emerging data have suggested progressive immunosuppression with lung cancer evolution that may have started at as early as preneoplastic states and continues to evolve with disease progression. These data advocate for immunotherapy of lung cancers at earlier stages. In addition to immunotherapy, chemotherapies, targeted agents, and radiation may also have a profound effect on the local immune contexture and mediate at least part of long-term effects by reinstating immunosurveillance. The presence of a pre-existing or induced immune response is often associated with more favorable prognosis. Future studies are required to depict the comprehensive molecular and immune evolution of lung cancers of different stages, both before and during treatment, to systematically understand the complex interaction between host immune system and cancer and eventually more effectively harness the immune system to combat lung cancers. Citation Format: Jianjun Zhang. Immune contexture evolution during lung cancer carcinogenesis and its potential clinical implications [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA35.