Dataset Information

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

ABSTRACT:

Introduction

Significant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches.

Methods

To investigate mechanisms associated with terminally exhausted T cells, we sorted and performed transcriptional profiling of CD8⁺ tumor-infiltrating lymphocytes (TILs) co-expressing the exhaustion markers PD-1 and TIM-3 from large-volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single-cell level, to identify potential mechanisms that underlie their dysfunctional phenotype.

Results

We identified novel dysregulated pathways in CD8⁺PD-1⁺TIM-3⁺ cells that have not been well studied in TILs; these include bile acid and peroxisome pathway-related metabolism and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression.

Discussion

Based on bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma.

SUBMITTER: Cameron CM

PROVIDER: S-EPMC10643547 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

Cameron Cheryl M CM Richardson Brian B Golden Jackelyn B JB Phoon Yee Peng YP Tamilselvan Banumathi B Pfannenstiel Lukas L Thapaliya Samjhana S Roversi Gustavo G Gao Xing-Huang XH Zagore Leah L LL Cameron Mark J MJ Gastman Brian R BR

Frontiers in oncology 20231030

<h4>Introduction</h4>Significant heterogeneity exists within the tumor-infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and may retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted T cell subpopulations critical to the improvement of therapeutic approaches.<h4>Methods</h ...[more]

PMID: 38023136

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Project description:Squamous cell carcinoma, which is a malignant tumor of the squamous epithelium, has been a major cause of morbidity and mortality worldwide. It is a major health problem across the world and among the most common cancers seen in both Indian men and women as can be gauged from the records of the National Cancer Registry Programme. This study was undertaken to analyze the spectrum of squamous cell carcinoma cases presenting at M.Y. Hospital, Indore, during 2 years between 2007 and 2008, to understand the morphological patterns of squamous cell carcinoma lesions and classify them into morphological categories given by International Classification of Diseases for Oncology (ICD-O, third edition), to analyze the anatomical site distribution pattern of squamous cell carcinoma lesions and categorize them in topographical classes given by ICD-O. Over a 2-year period, 959 cases were retrieved from the files of histopathology laboratory, department of pathology, M.G.M. Medical College, Indore. Out of total 959 cases, the maximum cases-290 (30.24 %)-of squamous cell carcinoma were found between the fourth and fifth decades of life. The frequency of squamous cell carcinoma in patients older than 30 years was 96.35 %, while in cases of less than 30 years, it was 03.65 %. Most of the reported cases of squamous cell carcinoma included invasive types (i.e., 94.3 %). Cases with distant metastasis constituted 4.7 %, while only 1 % were noninvasive or in situ. The frequency of squamous cell carcinoma presenting at our institution was highest among those involving the lip, oral cavity, and pharynx (56.50 %), followed by those involving female genital organs (30.24 %). The respective involvement of skin, digestive organs, and respiratory systems was 4.70, 3.86, and 2.40 % in decreasing order of frequency. Frequency was least (1.05 %) among the cases reported to show metastatic deposits of squamous cell carcinoma in lymph nodes. Regarding the topographical spectrum, the maximum number of cases (26.07 %) of squamous cell carcinoma encountered belonged to ICD-O category C-53 (i.e., cervix). Among the morphological categories, the most frequently encountered was that of squamous cell carcinoma, keratinizing (35.2 %).

Dataset Information

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

Introduction

Methods

Results

Discussion

Publications

A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.

Similar Datasets

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