TIM-3 expression identifies a distinctive PD-1 + follicular helper T cell subset, with reduced interleukin 21 production and B cell help function in ovarian cancer patients

Li, Li; Ma, Yan; Xu, Yungen; Maerkeya, Kamalibaike

doi:10.1016/j.intimp.2018.02.016

Cited by 17 publications

(18 citation statements)

References 32 publications

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“…However, Tim‐3 expression on T cells in patients with HPV positive cervical cancer was significantly reduced after surgery. Studies have shown that CD8+ T cells had overexpression of Tim‐3 in a variety of tumors, which promotes tumorigenesis 21‐24 . Therefore, we speculate that the increase of Tim‐3 + CD8+ T cells in HPV positive cervical cancer leads to the weakening of the tumor‐killing effect of CD8+ T, and then, promotes the occurrence of cervical cancer.…”

Section: Discussionmentioning

confidence: 87%

“…Studies have shown that CD8+ T cells had overexpression of Tim-3 in a variety of tumors, which promotes tumorigenesis. [21][22][23][24] Therefore, we speculate that the increase of Tim-3 + CD8+ T cells in HPV positive cervical cancer leads to the weakening of the tumor-killing effect of CD8+ T, and then, promotes the occurrence of cervical cancer. Tim-3 plays different roles in different cancers.…”

Section: Discussionmentioning

confidence: 93%

See 1 more Smart Citation

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

et al. 2021

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 93%

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

et al. 2021

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“…Recent studies demonstrated an important role of TIM-3 T cell exhaustion in cancer (44)(45)(46). Wu and colleagues investigated the expression of TIM-3 on peripheral CD4 + T and CD8 + T cells in ovarian cancer and showed elevated expression of TIM-3 in T cells were associated with advanced stage and a higher tumor grade (poorly differentiated) (44).…”

Section: Discussionmentioning

confidence: 99%

Patients with BRCA mutated ovarian cancer may have fewer circulating MDSC and more peripheral CD8+ T cells compared with women with BRCA wild‑type disease during the early disease course

et al. 2019

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Immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are associated with immunologic tolerance and poor prognosis in ovarian cancer (OvCa). We hypothesized that women with germline BRCA1 and BRCA2 mutation-associated (gBRCAm) OvCa would have fewer circulating immunosuppressive immune cells compared to those with BRCA wild-type (BRCAwt) disease during their early disease course (<5 years post-diagnosis) where gBRCAm is a favorable prognostic factor. We collected and viably froze peripheral blood mononuclear cells (PBMCs) from patients with recurrent OvCa olaparib clinical trials (NCT01445418/NCT01237067). Immune subset analyses were performed using flow cytometry for Tregs, exhausted CD8 + T cells, monocytes and MDSCs. Functional marker expression, including cytotoxic T lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain 3 (TIM-3) and programmed cell death protein 1 (PD-1) was evaluated. Data were analyzed using FlowJo. Pretreatment PBMCs were collected from 41 patients (16 gBRCAm/25 BRCAwt). The percentage of MDSCs among viable CD45 + PBMC was lower in gBRCAm OvCa compared with BRCAwt OvCa (median 0.565 vs. 0.93%, P=0.0086) but this difference was not seen in those women >5 years post-diagnosis. CD8 + T cells among viable CD45 + PBMCs and CTLA-4 + /CD8 + T cells were higher in gBRCAm carriers than patients with BRCAwt, in particular for those <5 years post-diagnosis (median 20.4 vs. 9.78%, P=0.031 and median MFI 0.19 vs. 0.22, P=0.0074, respectively). TIM-3 expression on Tregs was associated with poor progression-free survival, independent of gBRCAm status (P<0.001). Our pilot data suggested that patients with gBRCAm OvCa may have fewer circulating MDSCs but higher CD8 + T cells in PBMCs during their early disease course. This may contribute to the observed survival benefit for these women in their first post-diagnosis decade.

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“…Moreover, IL-21 was revealed to stimulate the expansion of CD8 + T cells and increase their cytotoxicity, which in turn promoted the proliferation and antibody production of T cell-dependent B cells; this induced the differentiation and activation of NK cells, and reduced the number of Treg cells in tumors (8,9). Previously, the application of recombinant human IL-21 to patients or animals has demonstrated significant antitumor activity in both nonclinical and clinical studies (10)(11)(12). Phase I and II clinical trials of IL-21 have been conducted in patients with renal cell carcinoma, non-Hodgkin's lymphoma and malignant melanoma (10)(11)(12); the results indicated that the therapeutic administration of IL-21 had a high validity and safety profile in patients (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

“…Previously, the application of recombinant human IL-21 to patients or animals has demonstrated significant antitumor activity in both nonclinical and clinical studies (10)(11)(12). Phase I and II clinical trials of IL-21 have been conducted in patients with renal cell carcinoma, non-Hodgkin's lymphoma and malignant melanoma (10)(11)(12); the results indicated that the therapeutic administration of IL-21 had a high validity and safety profile in patients (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Adenovirus‑mediated overexpression of interleukin‑21 regulates the development of oral squamous cell carcinoma in vitro

Liu

Sun

et al. 2020

Oncol Lett

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Interleukin-21 (IL-21) is an important cytokine that is currently being investigated for its potential use in tumor immunotherapy in the future. In tumor cells, IL-21 stimulates the immune response by increasing the cytotoxic activity of natural killer cells, B cells and CD8 + T cells, which in turn induces the apoptosis of tumor cells. The therapeutic effects of IL-21 have been investigated in several types of disease and numerous clinical trials are in progress. The aim of the present study was to determine the role of IL-21 in oral squamous cell carcinoma (OSCC) in vitro. IL-21 expression was detected in OSCC tissues via RT-qPCR, western blotting and immunohistochemistry analyses. The results demonstrated that IL-21 protein expression decreased in OSCC tissues. IL-21 was overexpressed using adenovirus in CAL-27 cells. The Cell Counting Kit-8 assay demonstrated that overexpression of IL-21 inhibited cell proliferation. Furthermore, overexpression of IL-21 inhibited cell migration, detected by the wound healing assay, and promoted cell apoptosis, detected by TUNEL staining and flow cytometry analysis. The results demonstrated that overexpression of IL-21 inhibited activation of the JNK signaling pathway. In conclusion, the findings of the present study suggest that IL-21 may function as a potent antitumor agent in OSCC.

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TIM-3 expression identifies a distinctive PD-1 + follicular helper T cell subset, with reduced interleukin 21 production and B cell help function in ovarian cancer patients

Cited by 17 publications

References 32 publications

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma

Patients with BRCA mutated ovarian cancer may have fewer circulating MDSC and more peripheral CD8+ T cells compared with women with BRCA wild‑type disease during the early disease course

Adenovirus‑mediated overexpression of interleukin‑21 regulates the development of oral squamous cell carcinoma in vitro

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