Magnesium deficiency is associated with some types of cancer, including breast, ovarian, and kidney cancer. Pre-clinical studies have demonstrated that, while inhibiting primary tumor growth, a low magnesium diet promoted tumor metastasis. The current literature on cancer and magnesium is incomplete and lacks large-scale controlled clinical trials. Additionally, any immunological mechanism describing how magnesium, or lack thereof, influences cancer growth and development remains unclear.
A recent study published in Cell has investigated the role of magnesium in the anti-tumor immune response. The authors found that a molecule called Lymphocyte function-associated antigen 1 (LFA-1) was a key regulator in the cancer development associated with magnesium deficiency. LFA-1 is an immune-stimulating marker found on the surface of different types of immune cells. Critical immune functions, including the migration and activation of CD8+ T cells, immune cells responsible for cancer cell killing, are dependent on LFA-1.
Like many proteins, LFA-1 regulation is dictated by conformational changes. Importantly, each conformational state of LFA-1 directly impacts the immune response. When closed/bent, LFA-1 prevents T cells immunity against cancer cells. However, when open/extended, LFA-1 can facilitate anti-tumor immunity.
The study describes the impact of magnesium on conformational changes in LFA-1. Specifically, the authors show that magnesium is required to adopt the open/extended conformational state. Importantly, this work demonstrates that magnesium promotes cytotoxicity, the process by which CD8+ T cells kill cancer cells.
The authors also investigated the impact of magnesium on response to two different types of immunotherapy, a chimeric antigen receptor-T (CAR T) cells and an immune checkpoint inhibitor (ICI). The authors performed a retrospective analysis on a cohort of B cell lymphoma patients treated with CD19-directed CAR T cells. Additionally, the researchers analyzed outcomes in a cohort of non-small cell lung cancer patients treated with an ICI combined with chemotherapy. Patients who experienced magnesium deficits were less responsive to therapy and had reduced survival compared to patients with normal magnesium levels.
The researchers conclude that magnesium significantly impacts the immune response by regulating T cell activities through influencing conformation changes in LFA-1. Because the data presented in this study is retrospective, the authors acknowledge that prospective clinical trials are needed to determine the clinical relevance of magnesium in cancer treatment regimens.
Sources: Scientific Reports, Oncologist, Kidney360, Biochim Biophys Acta, Cell, Front Immunol