scholarly journals PD-1+ CD8+ T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients

2014 ◽  
Vol 111 (7) ◽  
pp. 1391-1399 ◽  
Author(s):  
X Wu ◽  
H Zhang ◽  
Q Xing ◽  
J Cui ◽  
J Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Colorectal Cancer Patients ◽  
Draining Lymph Nodes

scholarly journals TCR sequencing analysis of cancer tissues and tumor draining lymph nodes in colorectal cancer patients

2019 ◽  
Vol 8 (6) ◽  
pp. e1588085 ◽  
Author(s):  
Tatsuo Matsuda ◽  
Eisaku Miyauchi ◽  
Yu-Wen Hsu ◽  
Satoshi Nagayama ◽  
Kazuma Kiyotani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Sequencing Analysis ◽  
Colorectal Cancer Patients ◽  
Cancer Tissues ◽  
Draining Lymph Nodes

scholarly journals Distribution of Regulatory T-Cells and Other Phenotypes of T-Cells in Tumors and Regional Lymph Nodes of Colorectal Cancer Patients

In Vivo ◽  
2020 ◽  
Vol 34 (2) ◽  
pp. 849-856
Author(s):  
KEISUKE KAZAMA ◽  
JUNYA OTAKE ◽  
TETSUTA SATOYOSHI ◽  
MANABU SHIOZAWA ◽  
NOBUHIRO SUGANO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Regional Lymph Nodes ◽  
Colorectal Cancer Patients

Correlation between driver mutation and immune microenvironment in colorectal cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15513-e15513
Author(s):  
Xiaochen Cai ◽  
Yuezong Bai ◽  
Xiaochen Zhao ◽  
Longgang Cui ◽  
Hui Chen
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Nk Cells ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Tumor Stroma ◽  
Wild Type ◽  
Colorectal Cancer Patients

e15513 Background: Immune checkpoint inhibitor (ICI) therapy has made great achievements, but ICI monotherapies show less effectiveness in colorectal cancer patients. Biomarker exploration have carried out from PD-L1 expression, neo-antigen, gene mutation, etc., but no satisfactory results have been obtained. Methods: Patients, Colorectal cancer patients. Methods, Multi-color immunohistochemistry (multi-IHC) was used to evaluate CD8+ T cells, macrophages and natural killer cell (NK cell) in tumors and tumor stroma. The Shapiro-Wilk method was used to test the normality of the data, and the t-test or Mann-Whitney U test was used according to the test results. A two-sided P < 0.05 was considered a significant difference. Results: The study included 72 colorectal cancer patients, including 26 female (36.7%) and 46 male (63.8%), with a median age of 59.5 (50-67.3). There were 6 patients (8.3%) with BRAF mutation, 43 patients (59.7%) with KRAS mutation, and 56 patients (77.8%) with TP53 mutation. The results of immunohistochemistry showed that, BRAF mutation Vs BRAF wild-type or KRAS mutation Vs KRAS wild-type, the number or proportion of CD8+ T cells, macrophages or NK cells in tumor and tumor stroma were not statistically different. For TP53 mutation Vs TP53 wild-type, the number and proportion of CD8+ T cells or macrophages in tumor and tumor stroma were not statistically different. There was no statistical difference in the number and proportion of NK cells in tumor. But, the median number of NK cells in tumor stroma was 345 Vs 129, p = 0.06, and the proportion of NK cells was 5.2% Vs 1.39%, p = 0.02. Conclusions: There is no significant change in the immune microenvironment of colorectal cancer patients with BRAF mutation and KRAS mutation. There are more NK cells in tumor stroma of colorectal cancer patients with TP3 mutation.

scholarly journals Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Yang ◽  
Sijin Cheng ◽  
Nan Luo ◽  
Ranran Gao ◽  
Kezhuo Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
T Cells ◽  
T Cell ◽  
Cancer Patients ◽  
Cd8 T Cells ◽  
Methylation Status ◽  
Effector Memory ◽  
Binding Motif ◽  
Colorectal Cancer Patients

Abstract Background Tumor-reactive CD8+ tumor-infiltrating lymphocytes (TILs) represent a subtype of T cells that can recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated. Results In this study, we segregate tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirms previous conclusions that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identifies a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers CD39 and CD103 being specifically demethylated. In addition, dynamic changes are observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor binding motif enrichment analysis identifies several immune-related transcription factors, including three exhaustion-related genes (NR4A1, BATF, and EGR2) and VDR, which potentially play an important regulatory role in tumor-reactive CD8+ T cells. Conclusion Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.

Novel CoupledCAR technology for treating colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2528-2528
Author(s):  
Lei Xiao ◽  
Song Li ◽  
Chengfei Pu ◽  
Zhiyuan Cao ◽  
Xinyi Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Complete Remission ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Tumor Tissue ◽  
Lentiviral Vectors ◽  
Safety And Efficacy ◽  
Pet Ct ◽  
Colorectal Cancer Patients

2528 Background: Chimeric antigen receptor (CAR) T cell therapy has made significant progress in the treatment of blood cancers such as leukemia, lymphoma, and myeloma. However, the therapy faces many challenges in treating solid tumors. These challenges include physical barriers, tumor microenvironment immunosuppression, tumor heterogeneity, target specificity, and limited expansion in vivo. Methods: We designed a CAR lentivirus vector that consisted of a humanized CD19-specific single-chain variable fragment (scFv), a 4-1BB costimulatory domain, and a CD3ζ signaling domain.The lentivirus was produced by transfecting HEK-293T cells with CAR lentiviral vectors and viral packaging plasmids. Patient’s CD3 T cells was cultured in X-VIVO medium containing 125U/mL 1interleukin-2 (IL-2), and transduced with CAR lentivirus at certain MOI 24h after stimulated by anti-CD3/CD28 magnetic beads. Transduction efficiency was evaluated at 7 to 9 days after CAR lentivirus transduction, and quality controls for fungi, bacteria, mycoplasma, chlamydia, and endotoxin were performed. After infusion, serial peripheral blood samples were collected, and the expansion and the cytokine release of CART cells were detected by FACS and QPCR,respectively. The evaluation of response level for patients were performed at month 1,month 3,and month 6 by PET/CT. Results: We engineered CoupledCAR T cells with lentiviral vectors encoding an anti-GCC (guanylate cyclase 2C) CAR molecule. To verify the safety and efficacy of CoupledCAR-T cells for treating solid tumors, we conducted several clinical trials for different solid tumors, including seven patients with colorectal cancer. These seven patients failed multiple rounds of chemotherapy and radiotherapy. In the clinical trial, the metastatic colorectal cancer patients were infused with autologous anti-GCC CoupledCAR-T cells range from 4.9×105/kg to 2.9×106/kg. We observed that CoupledCAR-T cells expanded significantly in the patients and infiltrated tumor tissue sites, demonstrating enhanced anti-tumor activities. PET/CT showed significant tumor shrinkage and SUV max declined, and the ongoing responses were monitored. Patient 3 achieved complete response and the best overall response rate (ORR, include complete remission, complete metabolic response, and partial response.) was 57.1% (4/7), complete remission (CR) rate was 14.3% (1/7). Conclusions: In conclusion, the clinical data demonstrated that CoupledCAR-T cells effectively expanded, infiltrated tumor tissue sites, and kill tumor cells in patients with colorectal cancer. We used immunotherapy to achieve complete remission in patients with advanced colorectal cancer for the first time. We are recruiting more colorectal cancer patients to further test the safety and efficacy of anti-GCC CoupledCAR T cells. Since our CoupledCAR technology is a platform technology, we are expanding it to treat other solid tumors using different target tumor markers.

High Expression of sLex Associated with Poor Survival in Argentinian Colorectal Cancer Patients

2014 ◽  
Vol 29 (1) ◽  
pp. e30-e39 ◽  
Author(s):  
Ariel Zwenger ◽  
Martin Rabassa ◽  
Sandra Demichelis ◽  
Gabriel Grossman ◽  
Amada Segal-Eiras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Normal Mucosa ◽  
Poor Survival ◽  
Primary Tumors ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph ◽  
Colorectal Cancer Patients

Aim Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. Methods Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. Results In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. Conclusions The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.

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