Iron is both, an essential compound for many metabolic processes, and
iron deficiency can impact on the proliferation of cells including lymphocytes but also
tumor cells. On the other hand, excess
iron-catalyzed radical formation can induce cellular toxicity which has been previously demonstrated for T cells in hereditary
iron overload. Despite these interconnections, little is known on the effects of clinically approved intravenous
iron supplements for curing
cancer-related
anemia, on T cell differentiation,
tumor proliferation, anti-
tumor T cell responses and, of clinical importance, on efficacy of
cancer immunotherapies. Herein, we analyzed the effects of intravenous
iron supplementation on T cell function and on the effectiveness of anti-
cancer chemotherapy with IL-2/
doxorubicin or
immunotherapy with checkpoint-inhibitor anti-PD-L1 in C57Bl/6N female mice with implanted E0771 mammary
carcinomas. We found that
iron application resulted to an increased availability of
iron in the tumor microenvironment and stimulation of
tumor growth. In parallel,
iron application inhibited the activation, expansion and survival of cytotoxic CD8+ T cells and of CD4+ T helper cells type 1 and significantly reduced the efficacy of the investigated anti-
cancer treatments. Our results indicate that
iron administration has a
tumor growth promoting effect and impairs anti-
cancer responses of
tumor infiltrating T lymphocytes along with a reduced efficacy of anti-
cancer therapies.
Iron supplementation in
cancer patients, especially in those treated with
immunotherapies in a curative setting, may be thus used cautiously and prospective studies have to clarify the impact of such intervention on the outcome of patients.