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

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.

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Immunological effects as a biomarker of chemotherapy in metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e14077 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e14077-e14077

Author(s):

Teruo Sasatomi ◽

Yutaka Ogata ◽

Hideaki Yamana ◽

Yoshito Akagi ◽

Kazuo Shirouzu

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Metastatic Colorectal Cancer ◽

Tumor Marker ◽

Cancer Patients ◽

The Other ◽

Anti Cancer ◽

Before And After ◽

Immunological Effects ◽

Colorectal Cancer Patients

e14077 Background: Many multiple anti cancer drugs regimens have been established for metastatic colorectal cancer recently. We investigated cellular immunoreaction of these patients to their cancer. Methods: 26 metastatic colorectal cancer patients have been started chemotherapies. Their PBMC 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 than half. 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 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. Conclusions: We found that the CTL/T reg ratio of PBMC in metastatic colorectal cancer patients were useful for prediction of the effect of chemotherapy.

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The relative change in regulatory T cells / T helper lymphocytes ratio as parameter for prediction of therapy efficacy in metastatic colorectal cancer patients

Oncotarget ◽

10.18632/oncotarget.22606 ◽

2017 ◽

Vol 8 (65) ◽

pp. 109079-109093 ◽

Cited By ~ 4

Author(s):

Tong Xu ◽

Jiezhen Lu ◽

Hanxiang An

Keyword(s):

Colorectal Cancer ◽

T Cells ◽

Regulatory T Cells ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

T Helper ◽

T Helper Lymphocytes ◽

Therapy Efficacy ◽

Colorectal Cancer Patients ◽

Relative Change

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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

European Journal of Cancer ◽

10.1016/j.ejca.2018.01.006 ◽

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

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22121 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22121-e22121 ◽

Cited By ~ 1

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.

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