Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Sample Collection
2.2. Multi-Parametric Flow Cytometry Analyses
2.3. Statistical Analyses
3. Results
3.1. CD8+ T Cell Subsets in Colorectal Cancer and Association with DFS
3.2. Immune Checkpoints and Association with Progression-Free Survival
3.3. Expression of Immune Checkpoints on FoxP3−Helios+/− CD8+ T cells
3.4. Association of IC-Expressing CD8+ T Cells with DFS
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CRC | Colorectal cancer |
CTLA-4 | Cytotoxic T-lymphocyte-associated protein 4 |
FoxP3 | Forkhead box P3 |
ICs | Immune checkpoints |
IDO1 | Indoleamine 2,3-Dioxygenase 1 |
LAG-3 | Lymphocyte-activation gene 3 |
NILs | Normal tissue-infiltrating lymphocytes |
NT | Normal tissues |
PBMC | Peripheral blood mononuclear cell |
PD-1 | Programmed cell death-1 |
DFS | Disease-free survival |
TCGA | The Cancer Genome Atlas |
TILs | Tumor-infiltrating lymphocytes |
TIM-3 | T-cell immunoglobulin and mucin domain-3 |
TME | Tumor microenvironment |
Treg | T regulatory cell |
TT | Tumor tissues |
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CRC Patients | |
---|---|
Number | 32 {22} § |
Median age {range} | 61 {31–96} |
Gender {Male: Female} | 23:9 |
TNM stage | |
I | 5 {1} § |
II | 9 {8} § |
III | 15 {11} § |
IV | 3 {2} § |
Tumor budding | |
Low | 11{7} § |
Intermediate | 11{7} § |
High | 10 {8} § |
Right/Left-sided | |
Left | 21 {14} § |
Right | 11 {8} § |
Tumor histological type | |
Adenocarcinoma NOS | 30 {20} § |
Mucinous | 2 {2} § |
Lymphovascular invasion(LVI) | |
Yes | 12 {11} § |
No | 20 {11}§ |
Molecular testing | |
KRAS mutations | 4 {2} § |
BRAF mutations | 1 {1} § |
MSI-H/dMMR | 4 {3} § |
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Alsalman, A.; Al-Mterin, M.A.; Murshed, K.; Alloush, F.; Al-Shouli, S.T.; Toor, S.M.; Elkord, E. Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients. Cancers 2022, 14, 3194. https://doi.org/10.3390/cancers14133194
Alsalman A, Al-Mterin MA, Murshed K, Alloush F, Al-Shouli ST, Toor SM, Elkord E. Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients. Cancers. 2022; 14(13):3194. https://doi.org/10.3390/cancers14133194
Chicago/Turabian StyleAlsalman, Alhasan, Mohammad A. Al-Mterin, Khaled Murshed, Ferial Alloush, Samia T. Al-Shouli, Salman M. Toor, and Eyad Elkord. 2022. "Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients" Cancers 14, no. 13: 3194. https://doi.org/10.3390/cancers14133194