The Costimulatory Activity of Tim-3 Requires Akt and MAPK Signaling and Its Recruitment to the Immune Synapse

Investigators examined the upstream signaling pathways that control Tim-3–mediated increases in phosphorylated S6 in T cells. They defined the localization of Tim-3 relative to the T cell immune synapse and its effects on downstream signaling.
[Science Signaling]
Kataoka, S., Manandhar, P., Lee, J., Workman, C. J., Banerjee, H., Szymczak-Workman, A. L., Kvorjak, M., Lohmueller, J., & Kane, L. P. (2021). The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse. Science Signaling, 14(687). https://doi.org/10.1126/scisignal.aba0717 Cite
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Cancer Immunotherapy: It’s Time to Better Predict Patients’ Response

The authors critically discuss current knowledge regarding predictive biomarkers for checkpoint inhibitor-based immunotherapy, highlight the missing/unclear links and emphasise the importance of characterising each neoplasm and its microenvironment in order to better guide the course of treatment.
[British Journal of Cancer]
Pilard, C., Ancion, M., Delvenne, P., Jerusalem, G., Hubert, P., & Herfs, M. (2021). Cancer immunotherapy: it’s time to better predict patients’ response. British Journal of Cancer, 1–12. https://doi.org/10.1038/s41416-021-01413-x Cite
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TIM-3 Drives Temporal Differences in Restimulation-Induced Cell Death Sensitivity in Effector CD8+ T Cells in Conjunction with CEACAM1

Investigators characterized the role of T cell immunoglobulin and mucin domain containing 3 (TIM-3) in restimulation-induced cell death regulation.
[Cell Death & Disease]
Lake, C. M., Voss, K., Bauman, B. M., Pohida, K., Jiang, T., Dveksler, G., & Snow, A. L. (2021). TIM-3 drives temporal differences in restimulation-induced cell death sensitivity in effector CD8 + T cells in conjunction with CEACAM1. Cell Death & Disease, 12(4), 1–17. https://doi.org/10.1038/s41419-021-03689-6 Cite
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Inhibition of Bruton’s Tyrosine Kinase as a Therapeutic Strategy for Chemoresistant Oral Squamous Cell Carcinoma and Potential Suppression of Cancer Stemness

Researchers investigated the effects of Bruton’s tyrosine kinase (BTK) on oncurrent chemoradiotherapy-resistant oral squamous cell carcinoma tissues (OSCC). The effect of ibrutinib, a first-in-class BTK inhibitor, was tested on stem cell-like OSCC tumorspheres.
[Oncogenesis]
Liu, S.-C., Wu, Y.-C., Huang, C.-M., Hsieh, M.-S., Huang, T.-Y., Huang, C.-S., Hsu, T.-N., Huang, M.-S., Lee, W.-H., Yeh, C.-T., & Lin, C.-S. (2021). Inhibition of Bruton’s tyrosine kinase as a therapeutic strategy for chemoresistant oral squamous cell carcinoma and potential suppression of cancer stemness. Oncogenesis, 10(2), 1–18. https://doi.org/10.1038/s41389-021-00308-z Cite
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COVID-19 Immune Signatures Reveal Stable Antiviral T Cell Function despite Declining Humoral Responses

The role of SARS-CoV-2-specific T cell immunity, its relationship to antibodies, and pre-existing immunity against endemic coronaviruses (huCoV), which has been hypothesized to be protective, were investigated in healthy donors, recovered, and active COVID-19 patients.
[Immunity]
Bonifacius, A., Tischer-Zimmermann, S., Dragon, A. C., Gussarow, D., Vogel, A., Krettek, U., Gödecke, N., Yilmaz, M., Kraft, A. R. M., Hoeper, M. M., Pink, I., Schmidt, J. J., Li, Y., Welte, T., Maecker-Kolhoff, B., Martens, J., Berger, M. M., Lobenwein, C., Stankov, M. V., … Eiz-Vesper, B. (2021). COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Immunity, 54(2), 340-354.e6. https://doi.org/10.1016/j.immuni.2021.01.008 Cite
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Galectin-9 Interacts with PD-1 and TIM-3 to Regulate T Cell Death and Is a Target for Cancer Immunotherapy

Scientist showed that PD-1 contributed to the persistence of PD-1+TIM-3+ T cells by binding to the TIM-3 ligand galectin-9 and attenuated Gal-9/TIM-3-induced cell death.
[Nature Communications]
Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W.-C., Hsu, J.-M., Cha, J.-H., Hsu, J. L., Chou, C.-W., Sun, X., Deng, Y., Chou, C.-K., Yu, D., & Hung, M.-C. (2021). Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nature Communications, 12(1), 832. https://doi.org/10.1038/s41467-021-21099-2 Cite
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Modulation of Immune Checkpoints by Chemotherapy in Human Colorectal Liver Metastases

Scientists investigated the impact of chemotherapy on the tumor immune microenvironment. They treated human liver metastases slices with 5-fluorouracil plus either irinotecan or oxaliplatin, then performed single-cell transcriptome analyses.
[Cell Reports Medicine]
Jabbari, N., Kenerson, H. L., Lausted, C., Yan, X., Meng, C., Sullivan, K. M., Baloni, P., Bergey, D., Pillarisetty, V. G., Hood, L. E., Yeung, R. S., & Tian, Q. (2020). Modulation of Immune Checkpoints by Chemotherapy in Human Colorectal Liver Metastases. Cell Reports Medicine, 1(9). https://doi.org/10.1016/j.xcrm.2020.100160 Cite
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Tim-3 Promotes Tube Formation and Decreases Tight Junction Formation in Vascular Endothelial Cells

Tim-3 was overexpressed in vascular endothelial HMVECs and HUVECs and in vitro assays were used to determine that Tim-3 promoted cell proliferation, migration, invasion and tube formation through activating cyclin D1, Ras homolog gene family member A and vascular endothelial growth factor receptor 2.
[Bioscience Reports]
Cong, Y., Wang, X., Wang, S., Qiao, G., Li, Y., Cao, J., Jiang, W. G., & Cui, Y. (n.d.). Tim-3 promotes tube formation and decreases tight junction formation in vascular endothelial cells. Bioscience Reports. https://doi.org/10.1042/BSR20202130 Cite
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Decrease of T-Cells Exhaustion Markers Programmed Cell Death-1 and T-Cell Immunoglobulin and Mucin Domain-Containing Protein 3 and Plasma IL-10 Levels after Successful Treatment of Chronic Hepatitis C

Researchers studied 76 DAA-treated hepatitis C virus (HCV)-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4+PD-1+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cells and IL-10 levels measured by ELISA were significantly higher and CD4+PD-1Tim-3 and CD8+PD-1−Tim-3 T-cells were significantly lower in patients than in controls.
[Scientific Reports]
Decrease of T-cells exhaustion markers programmed cell death-1 and T-cell immunoglobulin and mucin domain-containing protein 3 and plasma IL-10 levels after successful treatment of chronic hepatitis C | Scientific Reports. (n.d.). Retrieved September 30, 2020, from https://www.nature.com/articles/s41598-020-73137-6 Cite
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Collagen Promotes Anti-PD-1/PD-L1 Resistance in Cancer through LAIR1-Dependent CD8+ T Cell Exhaustion

Collagen-induced T cell exhaustion occured through the receptor LAIR1, which is upregulated following CD18 interaction with collagen, and induces T cell exhaustion through SHP-1.
[Nature Communications]
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Expression of Inhibitory Receptors on T and NK Cells Defines Immunological Phenotypes of HCV Patients with Advanced Liver Fibrosis.

Investigators found that advanced fibrosis patients had higher frequencies of >3 inhibitory receptor co-expression on NK cells.
[iScience]
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