scholarly journals Exercise-Induced Engagement of the IL-15/IL15Rα axis Promotes Anti-Tumor Immunity

2021 ◽  
Author(s):  
Dafna Bar-Sagi ◽  
Emma Kurz ◽  
Tanner Dalton ◽  
Sorin Shadaloey ◽  
Emily Vucic ◽  
...  
Keyword(s):  
T Cells ◽  
Aerobic Exercise ◽  
Cd8 T Cells ◽  
Intervention Strategies ◽  
Therapeutic Interventions ◽  
Murine Models ◽  
Immune Intervention ◽  
Exercise Induced ◽  
And Function ◽  
Exercise Oncology

Abstract Tumor-infiltrating immune cells play a central role in controlling cancer development and progression, as well as in responses to therapeutic interventions. However, the mechanisms that control their mobilization, composition, and function are not completely understood. Here, we show that aerobic exercise is sufficient to induce an intra-tumoral expansion of activated CD8 T cells and a reduction in tumor growth in murine models of pancreatic cancer. Specifically, exercise-induced spikes in epinephrine promote a systemic immune mobilization and accumulation of tumor-infiltrating IL15Rα+ CD8 T cells. This sub-population of activated CD8 T cells is responsible for the tumor protective and immune activating benefits of aerobic exercise, as both are abrogated in the context of IL-15 antagonism. Notably, the anti-tumor effect of aerobic exercise is potentiated by PD-1 blockade, suggesting a therapeutically exploitable link between an exercise-oncology axis and immune intervention strategies in a largely intractable disease.

Expression and function of NK cell receptors in CD8+ T cells

2001 ◽  
Vol 13 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Christopher W McMahon ◽  
David H Raulet
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Nk Cell ◽  
Cell Receptors ◽  
Nk Cell Receptors ◽  
And Function

Maintenance and Function of Human CD8+ T Cells and NK Cells in Humanized Mice

2014 ◽  
pp. 181-192
Author(s):  
Udo F. Hartwig ◽  
Maya C. André ◽  
Christian Münz
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Humanized Mice ◽  
And Function

scholarly journals Combining Photodynamic Therapy with Immunostimulatory Nanoparticles Elicits Effective Anti-Tumor Immune Responses in Preclinical Murine Models

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1470
Author(s):  
Ruben Victor Huis in ‘t Veld ◽  
Candido G. Da Silva ◽  
Martine J. Jager ◽  
Luis J. Cruz ◽  
Ferry Ossendorp
Keyword(s):  
T Cells ◽  
Photodynamic Therapy ◽  
Immune Responses ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Vaccination Strategy ◽  
Neutrophil Infiltration ◽  
Poly I:C ◽  
Murine Models ◽  
Human Papillomavirus 16

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8+ T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8+ T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8+ T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors.

scholarly journals Self–class I MHC molecules support survival of naive CD8 T cells, but depress their functional sensitivity through regulation of CD8 expression levels

2009 ◽  
Vol 206 (10) ◽  
pp. 2253-2269 ◽  
Author(s):  
Kensuke Takada ◽  
Stephen C. Jameson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Survival ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Class I ◽  
Class I Mhc ◽  
Mhc Molecules ◽  
T Cell Survival ◽  
And Function

Previous studies have suggested that naive CD8 T cells require self-peptide–major histocompatability complex (MHC) complexes for maintenance. However, interpretation of such studies is complicated because of the involvement of lymphopenic animals, as lymphopenia drastically alters naive T cell homeostasis and function. In this study, we explored naive CD8 T cell survival and function in nonlymphopenic conditions by using bone marrow chimeric donors and hosts in which class I MHC expression is absent or limited to radiosensitive versus radioresistant cells. We found that long-term survival of naive CD8 T cells (but not CD4 T cells) was impaired in the absence of class I MHC. However, distinct from this effect, class I MHC deprivation also enhanced naive CD8 T cell responsiveness to low-affinity (but not high-affinity) peptide–MHC ligands. We found that this improved sensitivity was a consequence of up-regulated CD8 levels, which was mediated through a transcriptional mechanism. Hence, our data suggest that, in a nonlymphopenic setting, self-class I MHC molecules support CD8 T cell survival, but that these interactions also attenuate naive T cell sensitivity by dynamic tuning of CD8 levels.

scholarly journals The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells following Respiratory Viral Infection

Cell Reports ◽  
2020 ◽  
Vol 31 (13) ◽  
pp. 107827 ◽  
Author(s):  
Kristen E. Pauken ◽  
Jernej Godec ◽  
Pamela M. Odorizzi ◽  
Keturah E. Brown ◽  
Kathleen B. Yates ◽  
...  
Keyword(s):  
T Cells ◽  
Viral Infection ◽  
Cd8 T Cells ◽  
Respiratory Viral Infection ◽  
Memory Cd8 T Cells ◽  
And Function
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