The interaction between the bone marrow microenvironment and leukemia cells enhances cell adhesion-mediated signals that can promote malignant hematopoietic cell survival and change normal hematopoiesis. Integrins, on the surface of leukemia cells, are involved in this interaction and mediate cell adhesion to integrin receptors of other cells and the extracellular matrix. Studies show that inhibition of several integrins affects leukemia cell migration or survival as well as sensitivity to chemotherapy. This review focuses on the expression and role of key arginine–glycine–aspartate acid (RGD)-binding (αvβ3, α5β1, αIIbβ3) and non-RGD-binding (α2β1, α4β1, α6β1, and αLβ2) integrins on leukemia cells and in the leukemia microenvironment and their potential targeting in leukemia treatment.

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The tumor microenvironment is composed of a diverse milieu of cells such as the stromal cells, various types of immune cells as well the neoplastic cells. Substantial research in the last few decades has provided a detailed picture of the nature and content of the tumor microenvironment. Apart from the diverse composition, the recent focus has been on the altered state of metabolism seen in the cells of the tumor microenvironment. Cancer cells show increased uptake of available nutrients, and they are also highly active in generating metabolic by-products, which creates a unique microenvironment. Such aggressive metabolism of cancer cells highly affects the viability and function of the surrounding cells, specially the immune cells. The nutrient-deprived tumor microenvironment along with toxic metabolic by-products hinders immune cell activation and fosters the generation of a tolerogenic immune response. The dynamic interaction between immune cells and the tumor microenvironment has proved to be a fertile area of research. This has led to the development of immunotherapy, which has been highly successful in treating malignancies. Metabolism plays a pivotal role in determining this interaction as evident from the increasing number of studies that have emerged in this new area of immunometabolism in the tumor microenvironment. In this review, we aim to summarize the current information on the metabolic pathways operational in the tumor microenvironment and the detailed mechanisms through which the function of tumor-infiltrating immune cells get affected by the tumor cells. The review also tries to outline the importance of exploring this area to design novel, targeted immunotherapy.

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