Cytotoxic T lymphocytes (CTLs) are critical in the elimination of infected or malignant cells and are emerging as a major therapeutic target. How CTLs recognize and kill harmful cells has been characterized in vitro but little is known about these processes in the living organism. Here we review recent insights into CTL-mediated killing with an emphasis on in vivo CTL biology. Specifically, we focus on the possible rate-limiting steps determining the efficiency of CTL-mediated killing. We also highlight the need for cell-based datasets that permit the quantification of CTL dynamics, including CTL location, migration, and killing rates. A better understanding of these factors is required to predict protective CD8 T cell immunity in vivo and to design optimized vaccination protocols.
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http://dx.doi.org/10.1016/j.it.2017.04.002 | DOI Listing |
Adoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins.
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October 2024
Center of Disease Immunity and Intervention, College of Medicine, Lishui University, Lishui, China.
Cytotoxic CD8 T lymphocytes (CTLs) have been implicated in the severity of COVID-19. The TCR-pMHC ternary complex, formed by the T cell receptor (TCR) and peptide-MHC (major histocompatibility complex), constitutes the molecular basis of CTL responses against SARS-CoV-2. While numerous studies have been conducted on T cell immunity, the molecular mechanisms underlying CTL-mediated immunity against SARS-CoV-2 infection have not been well elaborated.
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April 2024
State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China. Electronic address:
The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8 T lymphocytes (CD8 CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8 CTLs in mouse tumors and patients.
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February 2024
Department of Immunology & National Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College, Beijing, China.
Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing.
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February 2024
Department of Life Sciences, University of Siena, Siena, Italy.
The tumor microenvironment (TME) plays a central role in the pathogenesis of chronic lymphocytic leukemia (CLL), contributing to disease progression and chemoresistance. Leukemic cells shape the TME into a pro-survival and immunosuppressive niche through contact-dependent and contact-independent interactions with the cellular components of the TME. Immune synapse (IS) formation is defective in CLL.
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