Immune cells in the tumour: new routes of retinoids for chemoprevention and chemotherapeutics

Abstract

Retinoids, vitamin A and its natural and synthetic analogues have various functions, including being involved in cell proliferation and differentiation and participating in the formation of vertebrate morphology. In addition, they may activate certain tumour suppressor genes that then act as tumour inhibitors. In the past decades, retinoids have been regarded as promising chemotherapeutic and chemopreventive agents; however, their mechanisms are still not fully understood. Immune cells that participate in or are associated with the immune response play vital roles in the initiation and development of many cancers. Interestingly, recent studies have demonstrated that retinoids can also exert various effects on immune cells including macrophages, T cells and dendritic cells in tumour tissues to execute anti-tumour actions, providing new insights into chemoprevention and chemotherapeutics. In this review, we focus on the effects of retinoids on immune cells in the tumour, which may provide new approaches for antineoplastic strategies.

Figure 1

The structures of retinoids that are used in clinical and preclinical research. ATRA is widely used in the treatment of APL. Clinical trials suggested that 13‐cisRA could reduce the death of second aerodigestive tract tumours. β‐Carotene has been studied for the prevention of lung cancers. 9‐cisRA has the potential to prevent mammary and prostate cancer. TAC‐101 shows promise as a suppressor of tumour growth in the liver and decreases mortality in animal models of primary hepatocellular carcinoma and metastatic colon cancer. 4‐HPR is expected to be used to treat ovarian and colon cancer.

Figure 2

The components of the tumour micro‐environment. The tumour micro‐environment is the cellular environment composed of the overall composition of various cell types and extracellular matrix components. Interactions between neoplastic cells and other substances like immune cells, fibroblasts, cytokines, other stroma cells and extracellular matrix proteins frequently make a difference in the development of tumours. Immune cells include macrophages, T lymphocytes, DCs, polymorphonuclear leukocytes and B lymphocytes cells. The blood vessel is a must for tumour growth.

Figure 3

The role of retinoids in regulating immune cells. Retinoids promote the differentiation of macrophages, inhibit the recruitment and activation of TAMs and depress M2 polarization of macrophages. With regard to T lymphocytes, retinoids shape Th1/Th2 responses and suppress the development of Th17 cell response; retinoids and TGF‐β act synergistically to promote the generation and function of Treg cells. Also, RA signalling has an important role in the differentiation of Tm cells. Retinoids are responsible for the differentiation, maturation and function of DCs.