Regulatory T cells express Tumor Necrosis Factor Receptor 2 with the highest intensity among CD4+ T cells in the draining lymph nodes of breast cancer

Ghods, Atri; Mehdipour, Fereshteh; Shariat, Mahmoud; Talei, Abdolrasoul; Ghaderi, Abbas

doi:10.1016/j.molimm.2021.06.013

Cited by 14 publications

(7 citation statements)

References 25 publications

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“…TDLNs play an important role in inhibiting the spread of cancer [ 20 , 21 ] and have been found to be of pivotal importance in immunotherapy in recent years [ 45 ]. Tregs were found to be clustered in TDLNs in previous studies in cancer patients [ 46 , 47 ]. Theoretically, these cells should be positively correlated with those in tumors in terms of quantity and function [ 48 , 49 ], such as neutrophils [ 50 ].…”

Section: Discussionmentioning

confidence: 76%

Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer

Yan

Xiong

et al. 2022

BMC Gastroenterol

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Background The prognostic value of intratumor T regulatory cells (Tregs) in colorectal cancer (CRC) was previously reported, but the role of these cells in tumor draining lymph nodes (TDLNs) was less addressed. Methods A total of 150 CRC stages I-IV were retrospectively enrolled. Intratumor and TDLN Tregs were examined by immunohistochemical assay. The association of these cells was estimated by Pearson correlation. Survival analyses of subgroups were conducted by Kaplan–Meier curves, and the log-rank test and risk factors for survival were tested by the Cox proportional hazard model. Results High accumulation of Tregs in tumors was significant in patients with younger age and good histological grade, where enrichment of these cells in TDLNs was more apparent in those with node-negative disease and early TNM stage disease, both of which were more common in early T stage cases. A significant correlation of intratumoral and TDLN Tregs was detected. Patients with higher intratumoral Tregs displayed significantly better PFS and OS than those with lower Tregs. However, no such differences were found, but a similar prognostic prediction trend was found for these cells in TDLNs. Finally, intratumoral Tregs were an independent prognostic factor for both PFS (HR = 0.97, 95% CI 0.95–0.99, P < 0.01) and OS (HR = 0.98, 95% CI 0.95–1.00, P = 0.04) in the patients. Conclusions Higher intratumor Tregs were associated with better survival in CRC. Although no such role was found for these cells in TDLNs, the positive correlation and similar prognostic prediction trend with their intratumoral counterparts may indicate a parallelized function of these cells in CRC.

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Section: Discussionmentioning

confidence: 76%

Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer

Yan

Xiong

et al. 2022

BMC Gastroenterol

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“…TNFRSF1B transcription was alleviated obviously in Tregs in both tumor and TDLNs, regardless of lymph nodes with tumor invasion or not (52). There is also other evidence indicating that the majority of CD4 +CD25+Foxp3+ Tregs are TNFR2+, and they expressed TNFR2 with the highest intensity in the TDLNs of breast cancer, up to 90.5% ± 11.3%, when compared with other CD4+ T cells, which highlights the importance of TNFR2 in Tregs (53). However, they also found that most TNFR2+CD4+ T cells were Foxp3 −CD25− in the TDLNs.…”

Section: Tnfr2 Is Highly Expressed In Tregs and Essential For Functio...mentioning

confidence: 88%

Targeting TNFR2 in Cancer: All Roads Lead to Rome

Bai

Ding

2022

Front. Immunol.

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TNF receptor 2 (TNFR2) has become one of the best potential immune checkpoints that might be targeted, mainly because of its vital role in tumor microenvironments (TMEs). Overexpression of TNFR2 in some tumor cells and essential function in immunosuppressive cells, especially regulatory T cells (Tregs), makes blocking TNFR2 an excellent strategy in cancer treatment; however, there is evidence showing that activating TNFR2 can also inhibit tumor progression in vivo. In this review, we will discuss drugs that block and activate TNFR2 under clinical trials or preclinical developments up till now. Meanwhile, we summarize and explore the possible mechanisms related to them.

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“…Tumor-infiltrating regulatory T-cells are, with high frequency, strongly positive for TNFR2 [ 92 ]. For example, in breast cancer, acute myeloid leukemia (AML) and lung cancer, the highest TNFR2 expression levels were found on Foxp3 + CD25 + CD4 + Tregs [ 93 , 94 , 95 , 96 ]. Interestingly, there is evidence that chemotherapy affects the TNFR2 + Treg pool in triple-negative breast tumors more severely than the infiltrating CD8 + T-cells, so in this special treatment situation, the anti-tumoral TNFR2 activities prevail [ 97 ].…”

Section: Tnfr2 In Cancermentioning

confidence: 99%

Tumor Necrosis Factor Receptor 2 (TNFR2): An Emerging Target in Cancer Therapy

Medler

Kucka

Wajant

2022

Cancers

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Despite the great success of TNF blockers in the treatment of autoimmune diseases and the identification of TNF as a factor that influences the development of tumors in many ways, the role of TNFR2 in tumor biology and its potential suitability as a therapeutic target in cancer therapy have long been underestimated. This has been fundamentally changed with the identification of TNFR2 as a regulatory T-cell (Treg)-stimulating factor and the general clinical breakthrough of immunotherapeutic approaches. However, considering TNFR2 as a sole immunosuppressive factor in the tumor microenvironment does not go far enough. TNFR2 can also co-stimulate CD8+ T-cells, sensitize some immune and tumor cells to the cytotoxic effects of TNFR1 and/or acts as an oncogene. In view of the wide range of cancer-associated TNFR2 activities, it is not surprising that both antagonists and agonists of TNFR2 are considered for tumor therapy and have indeed shown overwhelming anti-tumor activity in preclinical studies. Based on a brief summary of TNFR2 signaling and the immunoregulatory functions of TNFR2, we discuss here the main preclinical findings and insights gained with TNFR2 agonists and antagonists. In particular, we address the question of which TNFR2-associated molecular and cellular mechanisms underlie the observed anti-tumoral activities of TNFR2 agonists and antagonists.

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Regulatory T cells express Tumor Necrosis Factor Receptor 2 with the highest intensity among CD4+ T cells in the draining lymph nodes of breast cancer

Cited by 14 publications

References 25 publications

Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer

Correlation and prognostic implications of intratumor and tumor draining lymph node Foxp3+ T regulatory cells in colorectal cancer

Targeting TNFR2 in Cancer: All Roads Lead to Rome

Tumor Necrosis Factor Receptor 2 (TNFR2): An Emerging Target in Cancer Therapy

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