The dynamic interplay between cellular immunity and tumor cells is essential in cancer advancement and response to therapy. This updated, comprehensive review examines the intricate relationship between these components, focusing on the function of different subsets of immune cells in both innate and acquired immunity. A literature search was conducted to ...

Graft-versus-host disease remains one of the most formidable barriers to the complete success of hematopoietic stem cell transplantation that has emerged as the curative approach for many hematopoietic malignancies because it affects quality of life and overall survival. Macrophages are among the important members of the immune system, which perform dual roles in GVHD as both therapeutic tools and targets. This review epitomizes the multifunctional role of macrophages in the pathophysiology of both acute and chronic GVHD. Macrophages play an important role in the early phase of GVHD because of their recruitment and infiltration into target organs. Furthermore, they polarize into two functionally different phenotypes, including M1 and M2. In the case of acute GVHD, most macrophages express the M1 phenotype characterized by the production of pro-inflammatory cytokines that contribute to tissue damage. In contrast, in chronic GVHD, macrophages tend toward the M2 phenotype associated with the repair of tissues and fibrosis. A critical balance among these phenotypes is central to the course and severity of GVHD. Further interactions of macrophages with other lymphocytes such as T cells, B cells, and fibroblast further determine the course of GVHD. Macrophage interaction associated with alloreactive T cells promotes inflammation. This is therefore important in inducing injuries of tissues during acute GVHD. Interaction of macrophages, B cell, fibroblast, and CD4+ T cells promotes fibrosis during chronic GVHD and, hence, the subsequent dysfunction of organs. These are some insights, while several challenges remain. First, the impact of the dominant cytokines in GVHD on the polarization of macrophages is incompletely characterized and sometimes controversial. Second, the development of targeted therapies able to modulate macrophage function without systemic side effects remains an area of ongoing investigation. Future directions involve the exploration of macrophage-targeted therapies, including small molecules, antibodies, and nanotechnology, which modulate macrophage behavior and improve patient outcomes. This underlines the fact that a profound understanding of the dual role of macrophages in GVHD is essential for developing new and more effective therapeutic strategies. Targeting macrophages might represent one avenue for decreasing the incidence and severity of GVHD and improving the success and safety of HSCT.

Acute myeloid leukemia (AML) remains a formidable blood cancer, despite recent advances in treatment. A significant challenge persists in improving patient outcomes, particularly in addressing relapse and treatment resistance. Identifying new therapeutic targets is critical for advancing AML therapy. C-type lectin-like molecule-1 (CLL-1) has emerged as a promising therapeutic target in AML. This cell surface receptor is highly expressed on AML blasts and demonstrates stable expression throughout disease progression. CLL-1’s consistent presence makes it an ideal candidate for monitoring minimal residual disease (MRD), which is a critical indicator for predicting relapse. Beyond its utility as a diagnostic marker, CLL-1 offers exciting potential in the development of immunotherapies. Emerging strategies, such as CAR-T-cell therapy and antibody-drug conjugates (ADCs), are being investigated to leverage the immune system against CLL-1-expressing AML cells. This review examines the structure, function, and expression patterns of CLL-1 in AML and other hematologic malignancies, providing insights into its role in disease pathogenesis and treatment potential. Exploring CLL-1 as a target for diagnosis, MRD monitoring, and immunotherapy opens new avenues for AML treatment. A deeper understanding of its relationship with AML pathogenesis will aid in the development of targeted therapies, offering hope for improved patient outcomes in the future.