HUMAN LEUKOCYTE ANTIGEN (HLA)-G: AS AN INVISIBILITY CLOAK FOR TUMOR CELLS IN HEMATOLOGICAL MALIGNANCIES

Abstract

Introduction: Hematological malignancies are a disease group that affects blood cells derived from myeloid or lymphoid lineage, resulting in impaired hematopoiesis. These neoplasms include mainly leukemias, lymphomas and multiple myeloma (MM). In these tumors, cancer cells adopt several mechanisms to evade the immune system and, thus, avoid their elimination. Among these mechanisms, HLA-G molecules have been the target of emerging studies on hematological malignancies, due to their tolerogenic and immunomodulatory function. Objective: Thus, the aim of this study is to perform a bibliographic review to report available data on HLA-G expression in hematological malignancies to demonstrate the possible correlations between HLA-G levels with the clinical outcomes in patients diagnosed with leukemia, lymphoma, or multiple myeloma. Material and methods: To perform this work, 14 English-written articles published between the years 2000 to 2023 were selected using the descriptors “HLA-G Antigens”, “Leukemia”, “Lymphoma”and “Multiple Myeloma”. We excluded articles outside the determined period or that addressed other hematological malignancy. Results and discussion: High soluble HLA-G (sHLA-G) concentration and membrane HLA-G expression were observed in patients with leukemia and lymphoma rather than healthy subjects. In MM cells, exhibiting higher HLA-G levels, there was more resistance to natural killer (NK) cell, cytotoxicity and robust mobilization of IL-10—producing dendritic cells (DC-10) and regulatory T cells (Treg). Since HLA-G promotes the inhibition of NK cells, T cells and other immune cells, besides modulating the cell plasticity towards a tumor-promoting phenotype these mechanisms may result from the observed relationship between poor clinical prognosis, therapy resistance, reduced survival and increased levels of HLA-G. Conclusion: It is concluded that HLA-G acts as an invisibility cloak, adopted by cancer cells for promoting immune escape. Therefore, HLA-G presents itself as a possible tumor biomarker of clinical prognosis. Funding: FAPEAM, CAPES and CNPq.