Vitamin A deficiency execrates Lewis lung carcinoma via induction of type 2 innate lymphoid cells and alternatively activates macrophages

Abstract

Background Lung carcinoma is still associated with high rates of morbidity and mortality despite the advances in cancer therapy achieved in last decades. Recent studies showed that immune responses played a crucial role in the developments of cancers including lung cancer. Type 1 immune response could promote classical activated macrophages (CAMs) with antitumor properties. On the contrast, type 2 immune response could lead to the polarization of alternatively activated macrophages (AAMs) which could promote the growth and metastasis of tumor. Our previous research showed that vitamin A deficiency could promote the type 2 immune response but not the type 1 immune response. Whether vitamin A deficiency has detrimental effect for lung carcinoma need further investigate. Aim To investigate the effect of vitamin A deficiency in lung cancer and the potential mechanisms. Methods Mice were fed with normal diet or vitamin A deficiency diet for 2 weeks, and then, Lewis lung cancer (LLC) cells dissolved in Matrigel Matrix were planted on the left lower lope of lungs. Mice were sacrificed 28 days after the plantation of tumor cells, the tumor size, cytokine profile in bronchoalveolar lavage fluid (BALF), numbers of type 2 innate lymphoid cells (ILC2s), and macrophage phenotypes in the lung were measured. The overall survival rate was also monitored throughout the experiments. Results Vitamin A deficiency diet fed tumor‐bearing mice have lower survival rate ( χ 2 = 6.862, p < 0.001), larger tumor size ( t = 2.651, p < 0.05), more ILC2s ( t = 7.680, p < 0.001), and AAMs ( t = 6.315, p < 0.001) in the lung tissue; also, type 2 cytokines concentrations in the BALF were higher compared to normal diet fed ones. Conclusion Vitamin A deficiency could promote the pathogeneses of lung carcinoma via induction of ILC2s and polarizing AAMs.

Vitamin A supplementation prevents the bronchopulmonary dysplasia in premature infants

“…Previous experiments [ 39 , 40 ] in rats have found that vitamin A has a significant effect on lung differentiation and maturation, mainly in the following two aspects. In contrast, lack of vitamin A can cause metaplasia of trachea and bronchial squamous epithelium, and supplementation of vitamin A-related agents can improve its morphological changes.…”

Vitamin A prevents lipopolysaccharide‐induced injury on tight junctions in mice

“…Applying VA deficiency model, Qi et al () explored novel changes of genes involved in nutrition metabolism and immune responses in growth retardation piglets. Cui et al () explored that VA deficiency enhances development of Lewis lung carcinoma through induction of type 2 innate lymphoid cells and activates macrophages. Thus, supplying VA could attenuate development of Lewis lung carcinoma by improving type 2 immune response (Cui et al, ).…”

“…Cui et al () explored that VA deficiency enhances development of Lewis lung carcinoma through induction of type 2 innate lymphoid cells and activates macrophages. Thus, supplying VA could attenuate development of Lewis lung carcinoma by improving type 2 immune response (Cui et al, ).…”

Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

“…The lactate production by melanoma cells may be considered a new therapeutic target to block tumor growth [ 153 ]. Recently, it has been demonstrated that Vit A deficiency induces the ILC2s infiltration of lung carcinoma with improved outcome, at least in the murine model [ 154 ]. If confirmed in the human setting, this discovery may provide a simple but effective strategy for the treatment of lung cancer.…”