Circulating regulatory T-cells and the clinical outcome of VEGF-targeted treatment of metastatic colorectal cancer patients: focused on KRAS status and primary tumour sidedness

2018 ◽  
Vol 92 ◽  
pp. S1-S2
Author(s):  
L. Zdrazilova-Dubska ◽  
E. Budinska ◽  
B. Bencsikova ◽  
K. Pilatova ◽  
R. Obermannova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Primary Tumour ◽  
Targeted Treatment ◽  
Kras Status ◽  
Colorectal Cancer Patients

CTLs/regulatory T-cells ratio as a prediction marker of chemotherapy in metastatic colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14684-e14684
Author(s):  
Teruo Sasatomi ◽  
Takafumi Oochi ◽  
Yutaka Ogata ◽  
Yoshito Akagi ◽  
Kazuo Shirouzu
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Metastatic Colorectal Cancer ◽  
Tumor Marker ◽  
Cancer Patients ◽  
Metastatic Lesion ◽  
The Other ◽  
Before And After ◽  
Colorectal Cancer Patients

e14684 Background: Many multiple anti cancer drugs regimens have been established for metastaticcolorectal cancer recently. We investigated cellular immunoreaction of these patients to their cancer. Methods: 32 metastatic colorectal cancer patients have been started chemotherapies. Their PBMCs were harvested and investigated their character by Fac scan with fluorescent labeled antibodies (CD3,CD8, CD4, CD25, Foxp3) at before and after chemotherapy. Results: After chemotherapy, both CTLs(CD3, CD8 positive) and regulatory T cells (CD4, CD25, Foxp3 positive) were decreased in number among all patients. On the other hand, CTL/T reg ratio were significantly increased among tumor marker decreased patients and significantly decreased among tumor marker increased or stable patients. CEA levels among 85.7% of increased CTL/T reg ratio patients became to decrease less thanhalf. CEA levels among 66.7% of decreased CTL/T reg ratio patients became to increase or to be stable, if their regimens have not been changed. The Reactive Rate of chemotherapy of CTL/T reg ratio increased patients was significantly higher than that of ratio decreased or stable patients. (P=0.021) The Disease Control Rate of chemotherapy of CTL/T reg ratio increased patients was higher than that of ratio decreased patients. Both resectability rate of liver metastatic lesion and early tumor shrinkage rate were higher at the CTL/T reg ratio increased patients group than at the other patients group. Conclusions: We found that the CTL/T reg ratios of PBMC in metastatic colorectal cancer patients were useful for prediction of the effect of chemotherapy.

Impact of antiangiogenic treatments on exhausted PD-1+ T lymphocytes in colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22121-e22121 ◽  
Author(s):  
Simon Pernot ◽  
Magali Terme ◽  
Elie Marcheteau ◽  
Thibault Voron ◽  
Orianne Colussi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Lymphocytes ◽  
Regulatory T Cells ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Kinase Inhibitors ◽  
Anti Vegf ◽  
Colorectal Cancer Patients

e22121 Background: Tumors develop immunosuppressive mechanisms to escape the immune system. Among these mechanisms, T lymphocytes can express inhibitory molecules such as Program Death-1 (PD-1) protein which impair their activation and their effector functions. Multi-target anti-angiogenic tyrosine kinase inhibitors (TKI) that are routinely used as first- or second-line treatment of cancer patients, have been shown to modulate immunosuppressive mechanisms especially regulatory T cells. However, the role of specific VEGF/VEGFR blockade on PD-1 expression by T lymphocytes has not been studied. Methods: PD-1 expression on T lymphocytes has been analyzed by flow cytometry in a mouse model of colorectal cancer (CT26) treated by anti-angiogenic molecules targeting the VEGF-A/VEGFR axis and in the peripheral blood of metastatic colorectal cancer patients. Results: Sunitinib that directly targets VEGFR, PDGFR, c-kit, but also anti-VEGF-A antibody (the mouse orthologue of bevacizumab) decrease PD-1 expression on T lymphocytes infiltrating the tumors. Interestingly, anti-angiogenic treatments decrease the percentage of lymphocytes expressing not only PD-1 but also Tim-3 suggesting that the most exhausted T cells are targeted by anti-angiogenic treatments. Administration of masitinib, a TKI acting on KIT, PDGFR and FAK but not on the VEGF/VEGF-R pathway, was not able to modulate PD-1 expression on T cells. Finally, anti-VEGF-A treatment (bevacizumab) associated with chemotherapy decreases the proportion of PD-1+ CD4+T cells in the peripheral blood of metastatic colorectal cancer patients. Conclusions: These results show that anti-angiogenic treatments targeting VEGFA/VEGFR decrease PD-1-expressing T lymphocytes in colorectal cancer. These results suggest that VEGF-A could be involved in PD-1 expression and maybe in the induction of T lymphocyte exhaustion in colorectal cancer. We and others have shown that anti-angiogenic molecules could modulate other immunosuppressive populations such as regulatory T cells and myeloid suppressive cells, anti-angiogenic molecules might be efficiently associated with immunotherapeutic strategies in colorectal cancer.

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

Colorectal cancer susceptibility variants and clinical outcome in adjuvant and metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4051-4051
Author(s):  
H. Lenz ◽  
G. Lurje ◽  
C. A. Haiman ◽  
D. Yang ◽  
A. Pohl ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Risk ◽  
Clinical Outcome ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Tumor Recurrence ◽  
Cancer Susceptibility ◽  
Locally Advanced ◽  
Germline Variants ◽  
Colorectal Cancer Patients

4051 Background: Recent genome-wide association studies had identified colorectal cancer susceptibility loci on chromosomes 8q24 (rs6983267), 15q13(rs4779584), 18q21(rs4939827, rs12953717 and rs4464148), 10p14(rs10795668) and 8q23.3(rs16892766). Although the function role of these germline variants are unclear, given the importance of these variants and colorectal cancer risk, we have carried out the first pilot study to explore the association of these variants and clinical outcome. We used pooled data from two CRC-cohorts (locally advanced and metastatic CRC), and investigated the hypothesis that these germline variants may be associated with clinical outcome in adjuvant and metastatic colorectal cancer patients. Methods: Whole blood was collected from 515 patients with locally advanced (n=197) and metastatic CRC (n=318). After extraction of genomic-DNA, germline variants were genotyped as previously described (Haiman et al, Nat Genet, 2007). The genotype success rate was 98%. Blinded repeat samples (5%) were included for quality control purposes; genotype concordance was ≥ 99%. Results: Our results suggest that rs10795668 at 10p14 and rs719725 are significantly associated with time to tumor recurrence in adjuvant colorectal cancer patients, patients with rs10795668 AA genotype had significantly increased risk of time to tumor recurrence compared with those harboring G allele (TG+GG) patients(p=0.05, log-rank test). In metastatic cancer patients, we found rs4939827 at 18q21.1 were significantly associated with overall survival in female patients and rs10795668 at 10p14 were significantly associated with OS in male patients, respectively (p<0.05). Conclusions: Our preliminary results suggest cancer risk alleles may also associated with clinical outcome in adjuvant and metastatic colorectal cancer. Moreover, this correlation is sex-specific in metastatic colorectal cancer. Further comprehensive trials warranted to confirm our pilot findings. [Table: see text]

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