galectin 9 t cells tim 3  (Galectin Therapeutics)

Journal: Biomarker Research

Article Title: Recent advances in systemic therapy for hepatocellular carcinoma

doi: 10.1186/s40364-021-00350-4

Figure Lengend Snippet: Mechanism of combination therapies. ( A ) Complementary mechanisms of PD-1/PD-L1 and CTLA-4 inhibitors. Presentation of tumor-associated antigen by the major histocompatibility complex (MHC) expressed by APCs results in the release of an activation signal in combination with a co-stimulatory signal via the B7-CD28 pathway, leading to activation of T cells in the lymph node; B7 also binds to CTLA-4 with a higher affinity than that of CD28, in which case T cells cannot be activated. PD-1 on T cells inhibits antigen-specific T cell activation by interacting with its ligands PD-L1 and PD-L2. Immune escape is induced through the PD-1/PD-L1 axis, as well as the B7/CTLA-4 axis. This figure was adapted from Kudo, et al. . ( B ) VEGF modulates the immunosuppressive TME, and TKIs restore this suppressive effect. Red arrows represent promotion effects. APCs, antigen presenting cells; CTL, cytotoxic T lymphocyte; CTLA-4, cytotoxic T-lymphocyte antigen 4; iDC, immature dendritic cell; matDC, mature dendritic cell; MDSCs, myeloid-derived stem cells; PD-1, programmed cell death protein 1; PD-L1, programmed cell death-ligand 1; TAMs, tumor-associated macrophages; TME, tumor microenvironment; Tregs, regulatory T cells. Note: This is an open access article distributed under the Creative Commons Attribution License that permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0)

Article Snippet: In addition to the well-known PD-1/PD-L1 and CTLA-4, a series of inhibitory immune checkpoint molecules involved in the immune tolerance of HCC have been reported, including lymphocyte activation gene 3 (LAG-3) [ ], T cell immunoglobulin mucin-3 (TIM-3)/galectin-9 (GLA-9) [ ], T cell immunoglobulin and ITIM domain (TIGHT) [ ], and adenosine A2a receptor.

Techniques: Immunopeptidomics, Activation Assay, Derivative Assay

Journal: Biomarker Research

Article Title: Recent advances in systemic therapy for hepatocellular carcinoma

doi: 10.1186/s40364-021-00350-4

Figure Lengend Snippet: Antibody-drug conjugates and bispecific T cell engagers for HCC treatment

Article Snippet: In addition to the well-known PD-1/PD-L1 and CTLA-4, a series of inhibitory immune checkpoint molecules involved in the immune tolerance of HCC have been reported, including lymphocyte activation gene 3 (LAG-3) [ ], T cell immunoglobulin mucin-3 (TIM-3)/galectin-9 (GLA-9) [ ], T cell immunoglobulin and ITIM domain (TIGHT) [ ], and adenosine A2a receptor.

Techniques:

Journal: Cancers

Article Title: Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

doi: 10.3390/cancers13071674

Figure Lengend Snippet: Principal mechanisms of immune evasion by CSCs/CICs. The immunomodulatory mechanisms by CSCs/CICs and the crosstalk with the TME that lead to impaired T cell-mediated responses are reviewed. The aberrant expression of multiple signaling pathways leads to the inefficient recognition and attack of CSCs/CICs by immune system. Among these pathways are: (1) the suboptimal expression of HLA molecules and APM, as well as of co-stimulatory molecules that cause the inability of T cells to recognize and kill the CSCs/CICs and their inefficient stimulation leading to their anergic/dysfunctional status; (2) the upregulation of the immune checkpoints, such as PD-1/PD-L1 and B7-H3 and the tryptophan catabolism by IDO that lead to impairment of effector T cell responses and the differentiation of immune suppressive immune cells (Tregs) and dysfunctional T lymphocytes); (3) the expression of pro-inflammatory cytokines (e.g., IL-6, IL-8, IL-10 and IL-13) and chemokines that drives the differentiation of immune cells toward suppressive subtypes (e.g., Tregs, M2 macrophages, MDSCs and iDCS); and (4) IFN-γ can play a dual effect in mediating both the anti-tumor effector functions and in up-modulating the negative regulator IDO. Moreover, TGFβ-1 in the TME can also regulate the expression of IDO. APM, antigen processing machinery; CSC/CIC, cancer stem cell/cancer initiating cell; HLA, human leukocyte antigen; iDC: immature and tolerogenic dendritic cells; IDO, Indoleamine 2,3- dioxygenase; IFN, interferon; IL-4, Interleukin 4; IL-6, Interleukin 6; IL-10, Interleukin 10; IL-13, Interleukin 13; MDSC, myeloid derived suppressor cell; M2 macrophages: immunomodulatory/suppressive macrophages; PD-1, programmed cell death 1; PD-L1, programmed cell death ligand 1; TME, tumor microenvironment; Treg, T regulatory cells.

Article Snippet: Leukemic-CSCs/CICs can also lead to the differentiation of MDSCs and TAM and the consequent impairment of T cells by the overexpression of T cell immunoglobulin mucin-3 (TIM-3)/Galectin 9 pathway [ , ].

Techniques: Expressing, Protein-Protein interactions, Derivative Assay

Journal: Cancers

Article Title: Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

doi: 10.3390/cancers13071674

Figure Lengend Snippet: The crosstalk between immune cells and CSCs/CICs.

Article Snippet: Leukemic-CSCs/CICs can also lead to the differentiation of MDSCs and TAM and the consequent impairment of T cells by the overexpression of T cell immunoglobulin mucin-3 (TIM-3)/Galectin 9 pathway [ , ].

Techniques: Expressing

Journal: Cancers

Article Title: Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

doi: 10.3390/cancers13071674

Figure Lengend Snippet: IDO is a key regulator of immunoregulatory properties of CSCs/CICs. IDO is a key regulator of anti-tumor immune responses. In an in vivo model (Panels ( A , B ), the expression of IDO in either tumor cells (Panel ( A )) or APC (Panel ( B )) can be induced by IFN-γ. IFN-γ can be released in the TME by effector cells activated through the engagement of TCR by HLA/peptide complexes expressed by either differentiated tumor cells (Panel ( A )) or APC (Panel ( B )). IFN-γ can then upregulate IDO in either CSCs/CICs or APC, leading to tryptophan degradation into kynurenine and its deprivation in the TME. Then, the inhibition of effector T cells and the differentiation of Tregs, MDSCs, M2 and iDCs occur, resulting in the impairment of efficient anti-CSC/CIC immune responses (Panels ( A ) and ( B ), respectively). The production of IDO by APC can also be mediated by the IFN-γ in either autocrine manner or when the cytokine is exogenously provided by components of the TME (Panel ( B )). The in vitro model can be utilized to assess the IFN-γ induced expression of IDO by CSCs/CICs and its role in inhibiting both the proliferation and the anti-CSC/CIC reactivity of T effector cells (Panel ( C )). T cell-mediated immune responses against CSCs/CICs can be rescued by neutralizing the activity of IDO with the specific inhibitor 1-MT (Panel ( D )). CSC/CIC, cancer stem cell/cancer initiating cell; HLA, human leukocyte antigen; iDC: immature and tolerogenic dendritic cell; IDO, indoleamine 2,3- dioxygenase; IFN, interferon; MDSC, myeloid derived suppressor cell; M2 macrophages: immunomodulatory/suppressive macrophages; TME, tumor microenvironment; Treg, T regulatory cells; 1-MT, 1- Methyl Tryptophan.

Article Snippet: Leukemic-CSCs/CICs can also lead to the differentiation of MDSCs and TAM and the consequent impairment of T cells by the overexpression of T cell immunoglobulin mucin-3 (TIM-3)/Galectin 9 pathway [ , ].

Techniques: In Vivo, Expressing, Inhibition, In Vitro, Activity Assay, Derivative Assay

Journal: Cancers

Article Title: Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

doi: 10.3390/cancers13071674

Figure Lengend Snippet: Immunomodulatory molecules in tumors and CSCs/CICs.

Article Snippet: Leukemic-CSCs/CICs can also lead to the differentiation of MDSCs and TAM and the consequent impairment of T cells by the overexpression of T cell immunoglobulin mucin-3 (TIM-3)/Galectin 9 pathway [ , ].

Techniques: Inhibition, Activity Assay

Journal: Cancers

Article Title: Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

doi: 10.3390/cancers13071674

Figure Lengend Snippet: The hallmarks of immune escape of CSCs/CICs. The immune privileged phenotype of CSCs/CICs is the result of aberrant genomic, epigenetic and post-transcriptional processes. Moreover, the interaction of multiple signaling pathways, either up-regulated or down-regulated, and the dynamic cross-talk between cancer cells and the TME drive the induction and maintenance of stemness functions, as well as the generation of immunosuppressive environment and immune evasion. Inside the CSC/CIC (in orange) are indicated the principal genomic, epigenetic and post-transcriptional mechanisms regulating the phenotypic make-up of CSCS/CICs. The major signaling pathways involved in the crosstalk between CSCs/CICs and TME are indicated in white inside the cell. The grey rounded rectangles represent the major processes regulating the interplay between stemness and TME/immune system. CIC, cancer initiating cell; CSC, cancer stem cell; EMT, epithelial-to-mesenchymal transition; IFN, interferon; PTEN, phosphatase and tensin homolog; STAT3, signal transducer and activator of transcription 3; TGF-β, transforming growth factor beta; TME, tumor microenvironment.

Article Snippet: Leukemic-CSCs/CICs can also lead to the differentiation of MDSCs and TAM and the consequent impairment of T cells by the overexpression of T cell immunoglobulin mucin-3 (TIM-3)/Galectin 9 pathway [ , ].

Techniques: Protein-Protein interactions