The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome

Abstract

Solid tumors, beyond mere accumulation of cancer cells, form a complex ecosystem consisting of normal epithelial cells, fibroblasts, blood and lymphatic vessels, structural components, and infiltrating hematopoietic cells including myeloid and lymphoid elements that impact tumor growth, tumor spreading, and clinical outcome. The composition of the immune microenvironment is diverse, including various populations of T cells, B cells, dendritic cells, natural killer cells, myeloid-derived suppressor cells, neutrophils, or macrophages. The immune contexture describes the density, location, and organization of these immune cells within solid tumors. In lung cancer, which is the deadliest type of cancer, and particularly in non-small cell lung cancer, its most prevalent form, reports have described some of the interactions between the tumor and the host. These data, in addition to articles on various types of tumors, provide a greater understanding of the tumor-host microenvironment interaction and stimulate the development of prognostic and predictive biomarkers, the identification of novel target antigens for therapeutic intervention, and the implementation of tools for long-term management of patients with cancer.

Keywords: immunotherapy; non–small cell lung cancer; prognosis; tumor immunology.

Figure 1.

The immune contexture of non–small cell lung cancer (NSCLC). The immune microenvironment of lung tumors is composed of T cells, B cells, natural killer (NK) cells, mature and immature dendritic cells (DCs), tumor-associated macrophages (TAMs), neutrophils, and mast cells. The great majority of immune cells are found at the interface between the tumor and the normal tissue, and some of them are organized in tertiary lymphoid structures (TLSs). The latter are considered a gateway for the entrance of immune cells from the blood to the tumor (via peripheral node addressin–expressing high endothelial venules [HEVs]). This process is highly regulated through chemokine/chemokine receptors, interleukins, integrins, and adhesion molecule expression or secretion. Ab = antibody; B = B cell; FDC = follicular dendritic cell; M = mast cell; mB = memory B cell; mDC = mature dendritic cell; N = neutrophil; PC = plasma cell; T = T cell; TAAs = tumor-associated antigens; T_FH = follicular helper T cell.