Determination of a CD4+CD25−FoxP3+ T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ

Jafarinia, Morteza; Mehdipour, Fereshteh; Hosseini, Seyed Vahid; Ghahramani, Leila; Hosseinzadeh, Massood; Ghaderi, Abbas

doi:10.1007/s13277-016-5345-y

Cited by 12 publications

(9 citation statements)

References 29 publications

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“…CD25 ¡ FoxP3 C cells in CRC patients showed lower suppressive and higher effector properties in comparison to the CD4 C CD25 C FoxP3 C nTregs. 41 Moreover, evidence accumulates that IL-10, produced by these CD25 ¡ Tregs, plays a pivotal role in preventing inflammation and hereditary colon cancer. 38 Instead, nTregs, isolated from PBMC of CRC patients, were capable of inhibiting anti-tumor immune responses.…”

Section: Discussionmentioning

confidence: 99%

Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation

et al. 2018

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Cancer-associated fibroblasts (CAFs) are involved in the proliferative and invasive behavior of colorectal cancer (CRC). Nonetheless, CAFs represent a heterogeneous population with both cancer-promoting and cancer-restraining actions, lacking specific markers to target them. Expression of the immune checkpoint molecule CD70 is normally limited to cells of the lymphoid lineage. Instead, tumor cells hijack CD70 to facilitate immune evasion by increasing the amount of suppressive regulatory T cells (Tregs). The aim of this study was to explore CD70 expression patterns in CRC, not merely focusing on the tumor cells, but also taking the tumor stromal cells into account. We have analyzed the prognostic value of CD70 expression by immunohistochemistry in CRC specimens and its relationship with well-known fibroblast markers and Tregs. In addition, experiments were conducted to unravel the role of CD70-positive CAFs on migration and immune escape. We reveal prominent expression of CD70 on a specific subset of CAFs in invasive CRC specimens. Cancer cells show almost no expression of CD70. The presence of CD70-positive CAFs proved to be an independent adverse prognostic marker. Functionally, CD70-positive CAFs stimulated migration and significantly increased the frequency of naturally occurring Tregs. In conclusion, we have identified the expression of CD70 on CAFs as a novel prognostic marker for CRC. We have found evidence of a cross talk between CD70 CAFs and naturally occurring Tregs, paving the way towards immune escape. As such, this study provides a strong rationale for the exploration of CD70-targeting antibodies in CRC.

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Section: Discussionmentioning

confidence: 99%

Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation

et al. 2018

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“…Larger numbers of Tregs in peripheral blood, TDLNs, and neoplasm tissues have been noted in CRC patients [ 8 , 20 , 21 ]. As has been demonstrated, most of the tumor-resident Tregs are thymus derived, while about half of the Treg population in nontumoral areas of the colon is induced Tregs (iTregs) which are generated in the periphery [ 22 ]. However, the role of Tregs in CRC is debatable [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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

Jie-zhen

2017

Oncotarget

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PurposeThe evaluation of regulatory T (Treg) (CD4+CD25high CD127neg) lymphocyte count with respect to the T helper (TH) (CD4) number has been shown to represent the main immune parameters capable of signifying the functional status of the anticancer immunity in cancer patients. This study is aimed to explore a correlation between therapy efficacy and changes in Treg/TH ratio and other biochemical and haematological parameters in patients with metastatic colorectal cancer (mCRC).Experimental DesignMeasurements of regulatory T cells were performed by flow cytometric analysis pre- and post-therapies in a prospective study.ResultsWe investigated levels of Treg/TH ratio in the peripheral blood of 25 mCRC patients pre- and post-chemotherapy ± targeted therapy. There were significant differences in levels of Treg/TH ratio pre- and post-treatments among patients on study, patients with partial response (PR), stable disease (SD) and progressive disease (PD) (P= 0.012, P= 0.011, and P= 0.043, respectively). Moreover, the relative change in Treg/TH ratio showed statistically significant difference among patients with PD as compared to those with PR and SD. Our findings demonstrated a statistically significant strong correlation between the relative change in Treg/TH ratio and therapeutic response. (Spearman's rho= 0.788/p<0.001).ConclusionsThe monitoring of the relative change in Treg/TH ratio could constitute a promising clinical index for response prediction and a timely change in regimen. Further prospective evaluations of these parameters investigated, particularly their association with overall survival, are warranted.

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“…They are either considered dysfunctional Treg cells, or activated effector T cells with transient expression of Foxp3 [77,80]. It has been suggested that CD4 + CD25 − FoxP3 + cells may be a heterogeneous population with effector or suppressive phenotype [81].…”

Section: Monofunctional T Cells (T Cells Produce Only One Cytokine)mentioning

confidence: 99%

Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck

et al. 2022

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Background A crucial role for the immune system has been proposed in the establishment and progression of head and neck squamous cell carcinoma (HNSCC). In this study, we investigated the cytokine and regulatory profiles of T cells in tumor draining lymph nodes (TDLNs) of patients with HNSCC. Results The frequencies of CD4+TNF-α+ and CD4+TNF-αhi negatively were associated with poor prognostic factors such as LN involvement (P = 0.015 and P = 0.019, respectively), stage of the disease (P = 0.032 and P = 0.010, respectively) and tumor size (P = 0.026 and P = 0.032, respectively). Frequencies of CD8+IFN-γ+ and CD8+IFN-γ+ TNF-α+ T cells showed negative relationship with tumor grade (P = 0.035 and P = 0.043, respectively). While, the frequencies of CD4+IL-4+, CD8+IL-10+, CD8+IL-4+T cells were higher in advanced stages of the disease (P = 0.042, P = 0.041 and P = 0.030, respectively) and CD4+IFN-γ+TNF-α−, CD8+IL-4+ and CD8+IFN-γ+TNF-α− T cells were higher in patients with larger tumor size (P = 0.026 and P = 0.032, respectively). Negative associations were found between the frequencies of CD4+CD25+Foxp3+ and CD4+CD25+Foxp3+CD127low/− Treg cells and cancer stage (P = 0.015 and P = 0.059). Conclusion This study shed more lights on the changes in immune profile of T cells in TDLNs of HNSCC. Larger tumor size and/or LN involvement were associated with lower frequencies of CD4+TNF-α+, CD8+IFN-γ+ and CD8+IFN-γ+TNF-α+ but higher frequency of CD4+IL-4+ T cells. Moreover, Foxp3+Tregs correlated with good prognostic indicators.

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Determination of a CD4+CD25−FoxP3+ T cells subset in tumor-draining lymph nodes of colorectal cancer secreting IL-2 and IFN-γ

Cited by 12 publications

References 29 publications

Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation

Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation

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

Regulatory and effector T cell subsets in tumor-draining lymph nodes of patients with squamous cell carcinoma of head and neck

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