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During pregnancy, complicated connections are formed between a mother and a fetus. In a successful pregnancy, the maternal-fetal interface is affected by dynamic changes, and the fetus is protected against the mother's immune system. Natural killer (NK) cells are one of the immune system cells in the female reproductive system that play an essential role in the physiology of pregnancy. NK cells not only exist in peripheral blood (PB) but also can exist in the decidua. Studies have suggested multiple roles for these cells, including decidualization, control of trophoblast growth and invasion, embryo acceptance and maintenance by the mother, and facilitation of placental development during pregnancy. Natural killer T (NKT) cells are another group of NK cells that play a crucial role in the maintenance of pregnancy and regulation of the immune system during pregnancy. Studies show that NK and NKT cells are not only effective in maintaining pregnancy but also can be involved in infertility-related diseases. This review focuses on NK and NKT cells biology and provides a detailed description of the functions of these cells in implantation, placentation, and immune tolerance during pregnancy and their role in pregnancy complications.

Salvia mirzayanii contains anti-hyperglycemic, antimicrobial, antioxidant, anti-inflammatory, and neuroprotective effects. The purpose of this study was to evaluate the anti-leishmanial efficacy of aqueous and alcoholic extracts of S. mirzayanii (both in vitro and in vivo) against Leishmania major. Aqueous and alcoholic extracts of S. mirzayanii were prepared and tested on L. major promastigotes and amastigotes. MTT test was used to evaluate the cytotoxicity of the plant against L. major. Flow cytometry was performed to assay apoptosis induced by 50 and 100 μg/ml of extracts on the promastigotes and macrophages. For the in vivo assay, the therapeutic effects of aqueous and alcoholic extracts of S. mirzayanii were tested in BALB/c mice. After 72 h, the IC50 value of aqueous and alcoholic extracts of S. mirzayanii against L. major promastigotes was 6.04 and 4.47, respectively. The inhibitory concentration (IC50) of aqueous and alcoholic extracts of S. mirzayanii to amastigotes were determined to be 47.78 μg/ml and 33.58 μg/ml, respectively. Flow cytometry revealed that the apoptosis of promastigotes using 100 μg/ml of aqueous and alcoholic extracts of S. mirzayanii was 5.81% and 5.39%, respectively, while apoptosis induced at 200 μg/ml were 5.09% and 70.71%, respectively. Lesion size was significantly decreased in in vivo experiments, and the survival rate of the treated mice improved in contrast to the control group. Given the efficacy of aqueous and alcoholic extracts of S. mirzayanii on promastigotes both in vitro and in vivo condition, the plant could be considered as a candidate source for the treatment of leishmaniosis.

Over the past few decades, different inhibitory receptors have been identified, which have played prominent roles in reducing anti-tumor immune responses. The role of immune checkpoint inhibitors in cancer was revealed by critical blockade of the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein-1 (PD-1) checkpoints. Immune checkpoint inhibitors, including anti-PD-1 (nivolumab and pembrolizumab), anti-PD-L1 (Atezolizumab, avelumab, and duravulumab), and anti-CTLA-4 (ipilimumab, tremelimumab), are currently FDA-approved treatment options for a broad range of cancer types. However, regarding immunotherapy advances in recent years, most studies have been focused on finding the antibodies against other inhibitory immune checkpoints in the tumor microenvironment such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin, and mucin domain 3 (TIM-3), B7-homolog 3 (B7-H3), V-domain immunoglobulin-containing suppressor of T-cell activation (VISTA), diacylglycerol kinase-α (DGK-α), T cell immunoglobulin and ITIM domain (TIGIT), and B and T lymphocyte attenuator (BTLA). This immune checkpoint exerts differential inhibitory impacts on various types of lymphocytes. The suppression of immune responses demonstrates a surprising synergy with PD-1. Therefore, most antibodies against these immune checkpoints are undertaking clinical trials for cancer immunotherapy of advanced solid tumors and hematologic malignancies. In this review, we will summarize recent findings of immune checkpoint and the role of monoclonal antibodies in cancer immunotherapy targeting these receptors.

During pregnancy, the fetal-maternal interface underlies several dynamic alterations to permit the fetus to be cultivated and developed in the uterus, in spite of being identifies by the maternal immune system. A large variety of decidual leukocyte populations, including natural killer cells, NKT cells, innate lymphoid cells, dendritic cells, B cells, T cells, subpopulations of helper T cells play a vital role in controlling the trophoblast invasion, angiogenesis as well as vascular remodeling. In contrast, several regulatory immunosuppressive mechanisms, including regulatory T cells, regulatory B cells, several cytokines and mediators are involved in maintain the homeostasis of immune system in the fetal-maternal interface. Nonetheless, aberrant alterations in the balance of immune inflammatory or immunosuppressive arms have been associated with various pregnancy losses and infertilities. As a result, numerous strategies have been developed to revers dysregulated balance of immune players to increase the chance of successful pregnancy. Lymphocyte immunotherapy has been developed through utilization of peripheral white blood cells of the husband or others and administered into the mother to confer an immune tolerance for embryo's antigens. However, the results have not always been promising, implying to further investigations to improve the approach. This review attempts to clarify the involvement of lymphocytes in contributing to the pregnancy outcome and the potential of lymphocyte immunotherapy in treatment of infertilities with dysregulated immune system basis.