Lung cancer: a classic example of tumor escape and progression while providing opportunities for immunological intervention

Abstract

Lung cancers remain one of the most common and deadly cancers in the world today (12.5% of newly diagnosed cancers) despite current advances in chemo- and radiation therapies. Often, by the time these tumors are diagnosed, they have already metastasized. These tumors demonstrate the classic hallmarks of cancer in that they have advanced defensive strategies allowing them to escape various standard oncological treatments. Immunotherapy is making inroads towards effectively treating other fatal cancers, such as melanoma, glioblastoma multiforme, and castrate-resistant prostate cancers. This paper will cover the escape mechanisms of bronchogenic lung cancer that must be overcome before they can be successfully treated. We also review the history of immunotherapy directed towards lung cancers.

Figure 1

Representative histological micrographs of the most common lung cancers. (a) Small-cell lung cancer taken with a 40x objective lens. (b) Squamous cell lung cancer visualized with a 40x objective lens. (c) Adenocarcinoma lung cancer seen using a 10x objective lens.

Figure 2

The four different types of CD4+ T cells. The different types of CD4 T cells start from common precursor T cells. Upon stimulation with the different cytokines, the naïve CD4+ cells now get to be selected by various transcription factors. Th1 cells become polarized towards this phenotype in response to IL-2 and IFN-γ, and the transcription factor, T-bet, now controls the fate of these cells. In response to IL-4 or IL-13, the Gata3 transcription factor becomes active and Th2 cells result. TGF-β now stimulates a common Th17/Treg cell. Upon stimulation with IL-6, IL-23, TGF-β, IL-1β (in humans), and PGE, Th17 cells become activated through a RORγT transcription factor. Tregs become polarized by FoxP3. The Tregs have the ability to inhibit Th1, Th2, and Th17 black arrows. The red arrows indicate the effector functions of the various CD4+ subsets. The side effects autoimmunity, allergies, or immune suppression are also noted.