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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Pan-cancer analysis of immune checkpoint receptors and ligands in various cells in the tumor immune microenvironment
Jiahuan Jiang1,2,3, Yazhang Xu1,3,4, Di Chen1,5
1Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou 310009, China.
Abstract:
Drugs that target immune checkpoint have become the most popular weapon in cancer immunotherapy, yet only have practical benefits for a small percentage of patients. Tumor cells constantly interact with their microenvironment, which is made up of a variety of immune cells as well as endothelial cells and fibroblasts. Immune checkpoint expression and blocked signaling of immune cells in the tumor microenvironment (TME) are key to tumor progression. In this study, we perform deliberation convolution on the TCGA database for human lung, breast, and colorectal cancer to infer crosstalk between immune checkpoint receptors (ICRs) and ligands (ICLs) in TME of pan-carcinogenic solid tumor types, validated by flow cytometry. Analysis of immune checkpoints showed that there was little variation between different tumor types. It showed that CD160, LAG3, TIGIT were found to be highly expressed in CD8+ T cells instead of CD4+ T cells, PD-L1, PD-L2, CD86, LGALS9, TNFRSF14, LILRB4 and other ligands were highly expressed on macrophages, FVR, NECTIN2, FGL1 were highly expressed on Epithelial cells, CD200 was highly expressed in Endothelial cells, and CD80 was highly expressed in CD8 High expression on T cells. Overall, our study provides a new resource for the expression of immune checkpoints in TME on various types of cells. Significance: This study provides immune checkpoint expression of immune cells of multiple cancer types to infer immune mechanisms in the tumor microenvironment and provide ideas for the development of new immune checkpoint-blocking drugs.
Insights
This study maps immune checkpoint expression across various cells in the tumor microenvironment (TME) for lung, breast, and colorectal cancers. Findings reveal cell-specific patterns, offering insights for novel cancer immunotherapy drug development.
Area of Science:
- Oncology
- Immunology
- Bioinformatics
Background:
- Cancer immunotherapies targeting immune checkpoints benefit only a subset of patients.
- Tumor microenvironment (TME) interactions are crucial for tumor progression.
- Understanding immune checkpoint expression in the TME is vital for improving cancer treatments.
Purpose of the Study:
- To analyze immune checkpoint receptor (ICR) and ligand (ICL) crosstalk in the TME of solid tumors.
- To provide a comprehensive resource on immune checkpoint expression across different cell types within the TME.
- To identify potential targets for new immune checkpoint-blocking drugs.
Main Methods:
- Deliberation convolution analysis of TCGA database for lung, breast, and colorectal cancers.
- Inference of ICR-ICL crosstalk within the TME.
- Validation using flow cytometry.
Main Results:
- Consistent immune checkpoint expression patterns were observed across different tumor types.
- Specific immune checkpoints like CD160, LAG3, and TIGIT were highly expressed on CD8+ T cells.
- PD-L1, PD-L2, and other ligands were highly expressed on macrophages, while epithelial cells, endothelial cells, and CD8+ T cells showed distinct expression profiles.
Conclusions:
- This study offers a valuable resource for understanding immune checkpoint expression in the TME.
- Identified cell-specific immune checkpoint patterns can inform the development of targeted cancer immunotherapies.
- The findings provide a basis for designing novel immune checkpoint-blocking drugs.
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