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

Food Sci Nutr. 2019 Feb 10;7(4):1288-1294. doi: 10.1002/fsn3.961. eCollection 2019 Apr.

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.

Keywords: ILC2; alternatively activated macrophages; cytokine; lung carcinoma; vitamin A.