Maintaining antitumor immunity remains a persistent impediment to cancer immunotherapy. We and others have previously reported that high-avidity CD8(+) T cells are more susceptible to tolerance induction in the tumor microenvironment. In the present study, we used a novel model where T cells derived from two independent TCR transgenic mouse lines recognize the same melanoma antigenic epitope but differ in their avidity. We tested whether providing CD4(+) T cell help would improve T cell responsiveness as a function of effector T cell avidity. Interestingly, delivery of CD4(+) T cell help during in vitro priming of CD8(+) T cells improved cytokine secretion and lytic capacity of high-avidity T cells, but not low-avidity T cells. Consistent with this observation, copriming with CD4(+) T cells improved antitumor immunity mediated by higher avidity, melanoma-specific CD8(+) T cells, but not T cells with similar specificity but lower avidity. Enhanced tumor immunity was associated with improved CD8(+) T cell expansion and reduced tolerization, and it was dependent on presentation of both CD4(+) and CD8(+) T cell epitopes by the same dendritic cell population. Our findings demonstrate that CD4(+) T cell help preferentially augments high-avidity CD8(+) T cells and provide important insight for understanding the requirements to elicit and maintain durable tumor immunity.
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http://dx.doi.org/10.4049/jimmunol.1401571 | DOI Listing |
Inflammation
December 2024
Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, Anhui, China.
Endoplasmic reticulum stress (ERs) is implicated in antitumor immunity. However, the exact role of ERs in mediating the effects of dendritic cells (DCs) is not unclear. In this study, we explored the role of exosomes derived from ER-stressed hepatocellular carcinoma (HCC) cells in the antitumor effects of DCs and the precise underlying mechanism.
View Article and Find Full Text PDFProbiotics Antimicrob Proteins
December 2024
Division of Gastroenterology, Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, 101, Daehak-Ro, Jongno-Gu, Seoul, Republic of Korea.
Pancreatic cancer is influenced by interactions between cancer cells and the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs). Specifically, CD8 + T cells impact prognosis by eliminating cancer cells. Recent studies have revealed that microbiomes are present in pancreatic tissues and may affect tumor growth and immune responses.
View Article and Find Full Text PDFImmunol Res
December 2024
Department of Respiratory Medicine, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.
This study aims to characterize the majority of immune cell subsets in peripheral blood mononuclear cells in children with Mycoplasma pneumoniae pneumonia (MPP) by a 21-color flow cytometry panel. Patients who met the predetermined eligibility criteria for pneumonia diagnosis were recruited for the research study. Multi-color flow cytometry was conducted on the peripheral blood mononuclear cells of each patient group, which were then subjected to dimensionality reduction and cluster analysis.
View Article and Find Full Text PDFMol Neurobiol
December 2024
Department of Physical Therapy, School of Health and Social Services, Saitama Prefectural University, 820 San-Nomiya, Koshigaya-Shi, Saitama, 343-8540, Japan.
Accumulation of senescent neurons in the dorsal root ganglion (DRG) is an important tissue phenotype that causes age-related degeneration of peripheral sensory nerves. Senescent neurons are neurons with arrested cell cycle that have undergone cellular senescence but remain in the tissue and play various biological roles. To understand the accumulation of senescent neurons in the DRG during aging, we aimed to elucidate the mechanism that induces cellular senescence in DRG neurons and the role of senescent DRG neurons.
View Article and Find Full Text PDFmBio
December 2024
Center for Vaccine Innovation, La Jolla Institute for Immunology (LJI), La Jolla, California, USA.
Frequent recent spillovers of subtype H5N1 clade 2.3.4.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!