Sa1161 INFLAMMATORY IMMUNE RESPONSES ASSOCIATED WITH ORAL IRON TREATMENT IN COLORECTAL CANCER PATIENTS WITH IRON DEFICIENCY ANAEMIA

Cancer has been described as an uncontrolled and rapid cell growth of mutated cells [1], with increasing incidence each year.Upon cancer initiation and progression, the immune system can play both anti-and pro-tumorigenic roles, depending on cell-cell interactions, as well as cellular changes of the immune cells in the tumor microenvironment [2].Amongst others, cell exhaustion, characterized by DNA damage, has been known to affect T cells and to lead to a worse outcome in colorectal cancer among various other cancer types [3].Specific mechanisms designed to protect T cells from further harm, such as p21 upregulation, regulate various processes once that DNA is damaged [3].However, the functional role of p21 in CD4+ T cells during colorectal cancer development has not yet been investigated.In order to study how p21 regulates various functions of CD4+ T cells in the tumor microenvironment, we employed an orthotopic tumor model in Rag-/-mice, which were reconstituted with either wildtype or p21-deficient T cells.Our results show that p21 loss in CD4+ T cells leads to an increased tumor growth.Functionally, p21-deficient T cells present in the tumor microenvironment influenced tumor cell growth, vascularity and neutrophil infiltration.Furthermore, reduced relative numbers of Tbet+CD4+ T cells are found at the tumor site.Similar data have been obtained by in vitro co-culturing p21deficient Th1 cells with MC38 cells, which resulted in decreased relative numbers of dying tumor cells compared to the ones cultured with wildtype Th1 cells.Further in vitro polarization experiments have shown that p21 is relevant for IFN g production.p21 loss also led to increased relative numbers of effector and memory cells, but decreased frequencies of CD28 expressing cells.Our findings on the gene expression revealed that Th1 cells lacking p21 have an increased expression of DNA repair gene BRCA1 as well.In conclusion, p21 mediates various processes such as IFN g production during T cell polarization.Changes in p21 expression in CD4+ T cells affected and modulated tumor initiation and progression, as well as immune infiltration, leading to increased carcinogenesis.p21 loss in CD4+ T cells leads to increased tumor growth.(A) Endoscopic images and H&E stainings showing tumor development in Rag-/-mice that were subjected to an orthotopic tumor model, after their immune system was reconstituted with either wildtype or p21-deficient (Cdkn1a-/-) CD4+ T cells (n ‡ 6 mice/group, *p<0.05).(B) Relative numbers of CD4+Tbet+ T cells in blood.mLN, spleen and tumor microenvironment of wildtype and p21-/-mice, as shown by flow cytometry data (**p<0.01).