Lung cancer and Toll-like receptors

Abstract

Lung carcinoma is one of the leading causes of death worldwide. It is a non-immunogenic cancer, resistant to immune surveillance. Toll-like receptors (TLRs) connect the innate to the adaptive immune system. Given that cancerous cells evade the immune system, the activation of TLRs could represent a potential target for cancer therapy. The induction of Th1-like and cytotoxic immunity by TLR signalling could lead to tumour cell death, resulting in tumour regression or arrest. However, basic research and clinical trials revealed that the activation of specific TLRs, such as TLR2, TLR4 and TLR9, do not have any anti-tumour activity in lung carcinoma. Increasing evidence suggests that TLRs are important regulators of tumour biology; however, little is known about their function in lung cancer. Thus, in order to develop new therapeutic approaches, further studies are needed to understand the connection between TLRs and lung cancer progression. This review focuses on the potential mechanisms by which TLR ligands can facilitate or not lung cancer and lung metastases establishment/progression.

Fig. 1

TLR signalling and their ligands

Fig. 2

The activation of Antigen Presenting Cells (APCs), such as DCs, mast cells and B cells, via TLRs can lead to differential adaptive immunity. The induction of a Th1-like as well as T cytotoxic (Tc)-like immunity leads to tumour regression, differently than a Th2-like and T reg-mediated immunity

Fig. 3

The activation of TLR2 (red arrows), TLR4 (black arrows) and TLR9 (blue arrows) on stromal cells can facilitate lung tumour progression by inducing the synthesis/release of both immune-suppressive cytokines, such as TGFβ and IL-10, which facilitate tumor progression, and extracellular matrix proteins and growth factors (i.e. VEGF, EGF and FGF2). Little is known about the role of TLR7 and TLR3 in lung carcinoma