Natural killer (NK) cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus-infected cells. NK cells show a broad array of tissue distribution and phenotypic variability. NK cells express several activating and inhibitory receptors that recognize the altered expression of proteins on target cells and control the cytolytic function. NK cells have been used in several clinical trials to control tumor growth. However, the results are encouraging only in hematological malignancies but not very promising in solid tumors. Increasing evidence suggests that tumor microenvironment regulate the phenotype and function of NK cells. In this review, we discussed the NK cell phenotypes and its effector function and impact of the tumor microenvironment on effector and cytolytic function of NK cells. We also summarized various NK cell-based immunotherapeutic strategies used in the past and the possibilities to improve the function of NK cell for the better clinical outcome.

γδ T cells represent a small population of overall T lymphocytes (0.5-5%) and have variable tissue distribution in the body. γδ T cells can perform complex functions, such as immune surveillance, immunoregulation, and effector function, without undergoing clonal expansion. Heterogeneous distribution and anatomic localization of γδ T cells in the normal and inflamed tissues play an important role in alloimmunity, autoimmunity, or immunity. The cross-talk between γδ T cells and other immune cells and phenotypic and functional plasticity of γδ T cells have been given recent attention in the field of immunology. In this review, we discussed the cellular and molecular interaction of γδ T cells with other immune cells and its mechanism in the pathogenesis of various autoimmune diseases.

cd T cells are an important innate immune component of the tumor microenvironment and are known to affect the immune response in a wide variety of tumors. Unlike ab T cells, cd T cells are capable of spontaneous secretion of IL-17A and IFN-c without undergoing clonal expansion. Although cd T cells do not require self-MHC-restricted priming, they can distinguish "foreign" or transformed cells from healthy self-cells by using activating and inhibitory killer Ig-like receptors. cd T cells were used in several clinical trials to treat cancer patient due to their MHC-unrestricted cytotoxicity, ability to distinguish transformed cells from normal cells, the capacity to secrete inflammatory cytokines and also their ability to enhance the generation of antigen-specific CD8 1 and CD4 1 T cell response. In this review, we discuss the effector and regulatory function of cd T cells in the tumor microenvironment with special emphasis on the potential for their use in adoptive cellular immunotherapy.gd T cells constitute a small proportion (< 5%) of T lymphocytes, and are different from conventional ab T lymphocytes. Most gd T cells recognize a wide variety of self-and nonself antigens such as metabolites of isopentenyl diphosphate (also known as phosphoantigens), small peptides, MHC-class I chain-related protein A (MICA), MHC-class I chain-related protein B (MICB) and mycobacterial heatshock proteins.

Background NKT cells play an important role in anti-tumor immunity. Alpha-galactosylceramide (α-GalCer), a synthetic glycolipid is presented to natural killer T (NKT) cells by most antigen-presenting cells through CD1d molecules leading to activation of NKT cells. However, the precise mechanisms of how α-GalCer-activated NKT regulate the polarization of the macrophages and effector T cells in the solid tumor are not studied adequately. Methods We induced solid tumor in C57BL/6 mice by subcutaneous injection of B16F10 cell line (1 X 10 6 cells) and monitored the tumor growth. Animals were given an intraperitoneal injection of α-GalCer (2 μg/injection) in 200 μl PBS on day + 1, + 5, + 10, + 15, and + 20 (with respect to tumor cell injection). Immune cells were characterized using flow cytometry and immunofluorescence staining. NK cells, Gr1 + cells, and F4/80 + macrophages in the mice were depleted by intravenous injection of cell-specific antibodies. Statistical analysis was performed using Student’s t -test or one-way ANOVA. Results Our results showed that intratumoral NKT cells have a lower frequency of CD69, CD25, CD122, and IFN-γR expression; produced less inflammatory cytokines such as IFN-γ, TNF-α, and GM-CSF; higher frequency CD62L + NKT cells; and also showed reduced proliferation as compared to the splenic NKT cells. Mice treated with α-GalCer showed a significantly increased frequency of IFN-γ-producing NKT cells, CD8 + T cells, and effector Th1 cells. Depletion of NK cells in α-GalCer-treated mice showed a lower frequency of IFN-γ-producing CD4 + and CD8 + T cells in the tumor and prevented the α-GalCer-induced tumor growth. NKT cell activation with α-GalCer treatment significantly increased the iNOS + CD206 − M1-macrophages and reduced the iNOS − CD206 + M2-macrophages in the spleen and tumor, and depletion of F4/80 + macrophages prevented the α-GalCer-induced reduction in the tumor growth. Conclusions We showed that activation of NKT cell with α-GalCer modulates the frequency of M1-macrophages and effector Th1 cells in the secondary lymphoid tissues and tumor microenvironment and inhibit tumor growth. The finding suggests that activation of NKT cells with α-GalCer may provide an effective anti-cancer outcome. Electronic supplementary material The online version of this article (10.1186/s40425-019-0697-7) contains supplementary material, which is available to authorized users.

Natural killer (NK) cells are known to have effector and cytolytic properties to kill virus infected or tumor cells spontaneously. Due to these properties, NK cells have been used as an adoptive cellular therapy to control tumor growth in various clinical trials but have shown limited clinical benefits. This indicates that our knowledge about phenotypic and functional differences in NK cells within the tumor microenvironment and secondary lymphoid tissues is incomplete. In this work, we report that B16F10 cellinduced melanoma recruits the CD11b C CD27C subset of NK cells at a very early stage during tumor progression. These intratumoral NK cells showed increased expression of CD69, reduced inhibitory receptor KLRG1, and decreased proliferative ability. As compared to splenic NK cells, intratumoral NK cells showed decreased expression of activating receptors NKG2D, Ly49D and Ly49H; increased inhibitory receptors, NKG2A and Ly49A; decreased cytokines IFNg and GM-CSF; decreased cytokine receptors IL-21R, IL-6Ra, and CD122 expression. Depletion of NK cells led to decrease peripheral as well as intratumoral effector CD4 C T-bet C cells (Th1), and increased tumor growth. Furthermore, purified NK cells showed increased differentiation of Th1 cells in an IFNg-dependent manner. Anti-NKG2D in the culture promoted differentiation of effector Th1 cells. Collectively, these observations suggest that intratumoral NK cells possess several inhibitory functions that can be partly reversed by signaling through the NKG2D receptor or by cytokine stimulation, which then leads to increased differentiation of effector Th1 cells.