Aim: To detect specific tumour infiltrating T cells (TIL) carrying antigen specific MHC-I restricted receptor genes on necrotising and non-necrotising malignant melanomas and to correlate the findings with clinical data.
Methods: alpha/beta- and gamma/delta- TIL were determined by immunohistochemical staining in melanomas of patients with known follow up of more than 10 years. An antigen retrieval method was used to determine variable genes delta1 and gamma1 on TCR(+) cells by an anti-TCR Vdelta1 and anti-CrgammaM1, and of Valpha and Vbeta TCR(+) by an anti-pan-TCR(+) alpha/beta antibody.
Results: Intratumoral TIL were present in 86 of 113 (76.1%) necrotising melanomas (NMM) v 21 of 100 (21%) in non-necrotising melanomas (MM); of these, Valpha/beta- TCR(+) cells were present in 52 of 74 (70.3%) TIL harbouring NMM v four of 21 (19%) MM; Vgamma1 in 29 of 74 (39.2%) NMM v two of 21 (10%) MM; and Vdelta1 in 39 of 74 (52.7%) NMM v three of 21 (14%) MM. Extratumoral lymphocytic infiltration was seen in 86 (76.1%) NMM including Valpha/beta TCR(+) cells in 10 (11.6%) cases, v five (5%) MM cases with no Valpha/beta TCR(+) cells detected. Vgamma1 and Vdelta1 TCR(+) cells were not found in extratumoral infiltrates.
Conclusions: In NMM, the median survival was 69.3 (range 6-237) months, 19 of 74 patients (25.7%) survived 5 years, and mortality was associated with advanced stage (p<0.001), patient age (p<0.023), and extent of necrosis (p<0.048). Survival was increased with evidence of Vgamma1 and Vdelta1 TCR(+) cells (p<0.026).
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http://dx.doi.org/10.1136/bjo.83.9.1069 | DOI Listing |
Front Immunol
January 2025
Center for Evolutionary and Theoretical Immunology, Department of Biology, University of New Mexico, Albuquerque, NM, United States.
Squamate reptiles are amongst the most successful terrestrial vertebrate lineages, with over 10,000 species across a broad range of ecosystems. Despite their success, squamates are also amongst the least studied lineages immunologically. Recently, a universal lack of γδ T cells in squamates due to deletions of the genes encoding the T cell receptor (TCR) γ and δ chains was discovered.
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January 2025
Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.
CD8T cells within the tumor microenvironment (TME) are often functionally impaired, which limits their ability to mount effective anti-tumor responses. However, the molecular mechanisms behind this dysfunction remain incompletely understood. Here, we identified valosin-containing protein (VCP) as a key regulator of CD8T cells suppression in hepatocellular carcinoma (HCC).
View Article and Find Full Text PDFPLoS Comput Biol
January 2025
Centre for Evolution and Cancer, Institute of Cancer Research, London, United Kingdom.
The applications of artificial intelligence (AI) and deep learning (DL) are leading to significant advances in cancer research, particularly in analysing histopathology images for prognostic and treatment-predictive insights. However, effective translation of these computational methods requires computational researchers to have at least a basic understanding of histopathology. In this work, we aim to bridge that gap by introducing essential histopathology concepts to support AI developers in their research.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Hepatobiliary Pancreatic Surgery.
T cells targeting a KRAS mutation can induce durable tumor regression in some patients with metastatic epithelial cancer. It is unknown whether T cells targeting mutant KRAS that are capable of killing tumor cells can be identified from peripheral blood of patients with pancreatic cancer. We developed an in vitro stimulation approach and identified HLA-A*11:01-restricted KRAS G12V-reactive CD8+ T cells and HLA-DRB1*15:01-restricted KRAS G12V-reactive CD4+ T cells from peripheral blood of 2 out of 6 HLA-A*11:01-positive patients with pancreatic cancer whose tumors expressed KRAS G12V.
View Article and Find Full Text PDFOncoimmunology
December 2025
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, Besançon, France.
Tissue-resident memory (T) T cells have emerged as key players in cancer immunosurveillance, and their presence has been linked to a favorable clinical outcome in solid cancer patients. Liver metastases exhibit a highly immunosuppressive tumor microenvironment, however, the role and clinical impact of T cell infiltration in colorectal cancer remain elusive. The expression of several tissue residency and activation biomarkers has been investigated on tumor-infiltrating lymphocytes isolated from 26 patients' colorectal cancer liver metastases (CRC liver metastases) and compared to 16 peripheral blood samples of patients with CRC liver metastases.
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