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.

Immune contexture and histological response after neoadjuvant chemotherapy predict clinical outcome of lung cancer patients

“…The role of tumor-associated macrophages is not fully understood in NSCLC and the presence of CD68 C macrophages has been associated with opposite prognostic values depending on the study. 9 To our knowledge, the prognostic value of CD68…”

“…8,9 Moreover, the concomitant presence of mature dendritic cells (DCs), reflecting the presence of tertiary lymphoid structures (TLS) within tumor tissues, identified group of patients with the best outcome. 10 Patients with advanced stages of the disease are mainly treated with neoadjuvant chemotherapy and the peculiar tumor microenvironment after such treatment remains poorly characterized.…”

Towards tumor immunodiagnostics

“…The lymphoid cells infiltrating the tumor may be organized in TLSs, consisting of B and T cell compartments, mimicking the lymph node structure and function (22,23). The B cell areas show lymphoid follicles with or without germinal center formation ( Figure 1D), including all the relevant constituents, namely, in addition to B cells at various stages of evolution, T follicular helper cells (Tfh), follicular dendritic cells (FDCs) and macrophages.…”

“…In the colon, they are usually noted around the muscularis propria or in the pericolic adipose tissue and because they are reminiscent of Crohn's disease they are called Crohn's-like reaction (CLR) (24,25). They are considered as tertiary lymphoid organs developing as part of the adaptive immune response to the tumor (25), are associated with prominent tumor infiltration by effectormemory CD8+ T cells and are considered important in educating CD8+ TILs in situ in order to control tumor growth (23,26,27).…”

“…TLSs have been associated with favorable outcome in breast (45) and lung carcinomas (23). In the colon, TLSs and CLR along with prominent lymphocytic infiltration (≥3 intraepithelial/intratumoral lymphocytes per high power field) are considered as evidence of high microsatellite instability (MSI-H), associated with favorable outcome (46).…”