Stem-like CD8 T cells (T) are a subset of immune cells with superior persistence and antitumor immunity. They are TCF1 PD-1 and important for the expansion of tumor specific CD8 T cells in response to checkpoint blockade immunotherapy. In acute infections, naïve CD8 T cells differentiate into effector and memory CD8 T cells; in cancer and chronic infections, persistent antigen stimulation can lead to T cell exhaustion. Recent studies have highlighted the dichotomy between late dysfunctional (or exhausted) T cells (T) that are TCF1 PD-1 and self-renewing TCF1 PD-1 T from which they derive. TCF1 T cells are considered to have stem cell-like properties akin to memory T cell populations and can give rise to cytotoxic effector and transitory T cell phenotypes (T) which mediate tumor control. In this review, we will discuss recent advances made in research on the formation and expansion of T, as well as distinct niches required for their differentiation and maintenance in the setting of cancer. We will also discuss potential strategies to generate these cells, with clinical implications for stemness enhancement in vaccine design, immune checkpoint blockade (ICB), and adoptive T cell therapies.
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http://dx.doi.org/10.3389/fimmu.2024.1426418 | DOI Listing |
J Immunother Cancer
January 2025
Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
Background: Oncolytic viruses (OVs) are promising immunotherapeutics to treat immunologically cold tumors. However, research on the mechanism of action of OVs in humans and clinically relevant biomarkers is still sparse. To induce strong T-cell responses against solid tumors, TILT-123 (Ad5/3-E2F-d24-hTNFa-IRES-hIL2, igrelimogene litadenorepvec) was developed.
View Article and Find Full Text PDFApoptosis
January 2025
Department of Breast Cancer Surgery, Jiangxi Cancer Hospital & Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Key Laboratory of Oncology, No. 519 Beijing East Road, Nanchang, Jiangxi, 330029, China.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Immunotherapy, a promising therapeutic approach, often faces challenges due to the immunosuppressive tumor microenvironment. This study explores the innovative use of CRISPR-Cas9 technology in conjunction with FCPCV nanoparticles to target and edit the C-C Motif Chemokine Ligand 5 (CCL5) gene, aiming to improve the efficacy of breast cancer immunotherapy.
View Article and Find Full Text PDFNat Immunol
January 2025
Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
BJC Rep
January 2025
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background: Osteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists' toxicity hinders this systemic approach in patients with osteosarcoma.
View Article and Find Full Text PDFCell Death Differ
January 2025
Laboratory of Hematology-Oncology, European Institute of Oncology IRCCS, Via Ripamonti 435, 20141, Milan, Italy.
Immunity suffers a function deficit during aging, and the incidence of cancer is increased in the elderly. However, most cancer models employ young mice, which are poorly representative of adult cancer patients. We have previously reported that Triple-Therapy (TT), involving antigen-presenting-cell activation by vinorelbine and generation of TCF1-stem-cell-like T cells (scTs) by cyclophosphamide significantly improved anti-PD-1 efficacy in anti-PD1-resistant models like Triple-Negative Breast Cancer (TNBC) and Non-Hodgkin's Lymphoma (NHL), due to T-cell-mediated tumor killing.
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