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.

Leukemia, a group of blood cancers, presents a significant global health challenge. Despite advancements in conventional therapies like chemotherapy and immunotherapy, the need for more effective and less toxic treatments remains. Nanotechnology offers a promising avenue for targeted drug delivery and immune modulation in the fight against leukemia. Through the utilization of nanomaterials’ special qualities, like their small size, large surface area, and capacity to transport a variety of payloads, scientists are creating novel ways to get around the drawbacks of conventional treatments. These strategies include targeted drug delivery, immune cell activation, and overcoming drug resistance. However, challenges remain in translating these promising nanotechnological approaches into clinical applications. Addressing issues such as toxicity, biodistribution, and regulatory hurdles is crucial for the successful development of nanomedicine for leukemia. In conclusion, nanotechnology offers a promising future for the treatment of leukemia. Continued research and development are essential to unlock the full potential of nanomaterials and improve patient outcomes. The potential of nanotechnology-based strategies to improve the effectiveness of leukemia treatments is explored in this review. We go over the function of different nanomaterials in delivering therapeutic agents to leukemia cells, such as liposomes, polymeric nanoparticles, and inorganic anoparticles. We also investigate the engineering of nanomaterials to influence the immune system and promote anti-tumor reactions.

Graft-versus-host disease (GVHD), a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT), is shaped by a dynamic interplay between two microbial ecosystems: the recipient's disrupted microbiome and the donor's transplanted microbiota. This narrative review unravels the "tale of two ecosystems," exploring how pre-transplant chemotherapy, radiation, and antibiotics induce recipient dysbiosis-marked by loss of beneficial taxa (Clostridia, Faecalibacterium) and dominance of pathobionts (Enterococcus). These shifts impair barrier integrity, fuel systemic inflammation, and skew immune responses toward pro-inflammatory T-cell subsets, exacerbating GVHD. Conversely, emerging evidence implicates donor microbiota in modulating post-transplant immune reconstitution, though its role remains underexplored. Therapeutic strategies, including probiotics, prebiotics, and fecal microbiota transplantation (FMT), demonstrate promise in restoring microbial balance, enhancing short-chain fatty acid (SCFA)-driven immune regulation, and reducing GVHD severity. However, challenges such as strain-specific efficacy, safety in immunocompromised hosts, and protocol standardization persist. By bridging microbial ecology and immunology, this review underscores the microbiome's transformative potential in redefining GVHD management and advocates for personalized, microbiome-targeted interventions to improve HSCT outcomes.

Acute myeloid leukemia (AML) remains a high-mortality cancer due to its aggressive nature and immunosuppressive tumor microenvironment (TME), which enables evasion of immune surveillance. Despite chemotherapy and targeted therapies, 5-year survival is ~ 30%, necessitating novel immunotherapies. AML suppresses cytotoxic T/NK cells by co-opting regulatory pathways, creating an “immune paradox.” Emerging strategies aim to disrupt this evasion. Immune checkpoint inhibitors (ICIs), such as anti-PD-1 nivolumab and anti-CD47 magrolimab, combined with hypomethylating agents (HMAs), enhance T-cell activity and phagocytosis, especially in TP53-mutated AML. Therapeutic vaccines targeting leukemia-associated antigens (e.g., WT1, PRAME) via dendritic cell fusion show early success in prolonging remission. Combinatorial approaches, like HMAs with STING agonists or dual checkpoint blockade, target multiple immunosuppressive pathways to overcome resistance. Challenges include TME heterogeneity, therapy-resistant leukemia stem cells, toxicities (e.g., anemia, cytokine release syndrome), relapse from clonal evolution, and a lack of predictive biomarkers. Autologous therapies face economic and logistical hurdles, driving demand for scalable solutions. Advances in single-cell genomics, AI, and synthetic biology are identifying novel targets (TIM-3, TIGIT, VISTA) and improving patient stratification. Integrating these innovations may transform AML into a chronic condition, bridging preclinical potential to clinical impact. In this review, we aim to evaluate mechanisms, challenges, and future directions of immunotherapies in AML with highlighting ICIs and vaccination to improve therapeutic outcomes.

Acute myeloid leukemia (AML), a heterogeneous and aggressive hematologic malignancy, remains challenging to treat due to high relapse rates, chemotherapy resistance, and the immunosuppressive tumor microenvironment (TME). While traditional therapies like chemotherapy and hematopoietic stem cell transplantation have improved outcomes, their efficacy is often limited by toxicity and disease recurrence. Recent advancements in antibody engineering have revolutionized AML immunotherapy, offering precision-targeted strategies to overcome these barriers. This narrative review explores the transformative role of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and bispecific antibodies (bsAbs) in redirecting immune effector cells, blocking immune checkpoints, and eradicating leukemic stem cells (LSCs). Key innovations include CD33-targeted gemtuzumab ozogamicin, CD123-directed bispecific engagers, and anti-CD47 agents that disrupt "don't eat me" signals. We highlight breakthroughs in antibody design-such as Fc optimization, trispecific constructs, and conditionally active biologics-that enhance specificity while minimizing on-target off-tumor toxicity. Clinical trials demonstrate promising results, including improved remission rates and survival in refractory/relapsed AML when combining antibodies with hypomethylating agents, venetoclax, or checkpoint inhibitors. However, challenges persist, including AML's genetic heterogeneity, adaptive immune evasion, and cytokine release syndrome (CRS) risks. Emerging strategies such as biomarker-driven personalization, TME modulation, and engineered NK-cell engagers are poised to address these limitations. By integrating preclinical insights with clinical data, this review underscores the potential of antibody-based combinatorial regimens to redefine AML therapy, offering durable responses and bridging the gap to curative approaches.