Regulatory T cells: balancing protection versus pathology

Rakebrandt, Nikolas; Littringer, Katharina; Joller, Nicole

doi:10.4414/smw.2016.14343

Cited by 21 publications

(20 citation statements)

References 76 publications

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“…The role of FoxP3C regulatory T cells (Tregs) in cancer remains highly controversial. 8,16 Whether it is part of an immunosuppressive network promoting tumor immunity or a protective mechanism controlling cancer-associated inflammation or both is still under investigation. One pooled analysis including 17 types of cancer (15512 cancer cases) suggested FoxP3CTregs had a significant negative effect on OS (OR 1.46, P < 0.001).…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy

Ou¹,

Adam

Garberis

et al. 2017

OncoImmunology

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To investigate the prognostic value of tumor infiltrating lymphocytes (TILs: CD8+ and FoxP3+), and PD-L1 expression in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy combined with cisplatin (CRT) or cetuximab (BRT). Immunohistochemistry for CD8, FoxP3 was performed on pretreatment tissue samples of 77 HNSCC patients. PD-L1 results were evaluable in 38 patients. Cox regression analysis was used to analyze the correlations of these biomarkers expression with clinicopathological characteristics and treatment outcomes. High CD8+ TILs level was identified in multivariate analysis (MVA) as an independent prognostic factor for improved progression-free survival with a non-significant trend for better overall survival (OS). High FoxP3+ TILs and PD-L1+ correlated with a favorable OS in the uni-variate analysis, respectively, but not in the MVA. In subgroup analysis, CD8+TILs appear to play a pivotal role, p16+/high CD8+TILs patients had superior 5-year OS compared with p16+/low CD8+TILs, p16-/ high CD8+TILs, and p16-/ low CD8+TILs patients. p16+/PD-L1+ patients had improved 3-year OS compared with p16+/PD-L1-, p16-/ PD-L1+, and p16-/ PD-L1- patients. In low CD8+ TILs tumors, 5-year loco-regional control of patients treated with CRT was improved vs. those with BRT (p = 0.01) while no significant difference in high CD8+ TILs was observed. CD8+ TILs correlated with an improved clinical outcome in HNSCC patients independent of Human papillomavirus status. The immunobiomarkers may provide information for selecting suitable patients for cisplatin or cetuximab treatment. Additionally, the impact of TILs and PD-L1 of deciphering among the p16+ population a very favorable outcome population could be of interest for patients tailored approaches.

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Section: Discussionmentioning

confidence: 99%

Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy

Ou¹,

Adam

Garberis

et al. 2017

OncoImmunology

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“…Accurately defining Tregs is, however, a challenge. Although there are several useful reviews available that highlight different markers and cytokines that may help identifying Tregs, there is no unique Treg marker (7,22,24,(173)(174)(175). Expression of FoxP3, the master regulator of classical CD4 + Tregs, is not limited to human regulatory cells: effector T cells transiently upregulate FoxP3 expression after activation and also other immune cells and even tumour cells may express this transcription factor (176)(177)(178)(179)(180)(181).…”

Section: Identifying Tregsmentioning

confidence: 99%

“…On the other hand, this suppressive activity may prevent pathogen clearance during infections and hinder effective immune responses against (mutated) self-antigens in cancer (20). Therefore, in diseases where the balance between immune activation and suppression is skewed, Tregs could be attractive pharmacological targets (21,22). For Th1-and Th17-dominated auto-immune disorders and Th2-dominated allergies, a therapy increasing Treg suppressive activity is sought (21,23,24).…”

Section: Introductionmentioning

confidence: 99%

Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised

2020

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Regulatory T cells (Tregs) have a prominent role in the control of immune homeostasis. Pharmacological impact on their activity or balance with effector T cells could contribute to (impaired) clinical responses or adverse events. Monitoring treatmentrelated effects on T cell subsets may therefore be part of (pre-)clinical studies for medicinal products. However, the extent of immune monitoring performed in studies for marketing authorisation and the degree of correspondence with data available in the public domain is not known. We evaluated the presence of T cell immunomonitoring in 46 registration dossiers of monoclonal antibodies indicated for immune-related disorders and published scientific papers. We found that the depth of Treg analysis in registration dossiers was rather small. Nevertheless, data on treatment-related Treg effects are available in public academia-driven studies (post-registration) and suggest that Tregs may act as a biomarker for clinical responses. However, public data are fragmented and obtained with heterogeneity of experimental approaches from a diversity of species and tissues. To reveal the potential added value of T cell (and particular Treg) evaluation in (pre-)clinical studies, more cell-specific data should be acquired, at least for medicinal products with an immunomodulatory mechanism. Therefore, extensive analysis of T cell subset contribution to clinical responses and the relevance of treatment-induced changes in their levels is needed. Preferably, industry and academia should work together to obtain these data in a standardised manner and to enrich our knowledge about T cell activity in disease pathogenesis and therapies. This will ultimately elucidate the necessity of T cell subset monitoring in the therapeutic benefit-risk assessment.

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“…Th17 cells are CD4 + T effector cells that produce a large amount of interleukin-17 (IL-17) which is a pro-inflammatory cytokine that attracts and activates granulocytes and monocytes [15]. The role of Th17 cells in cancer is controversial.…”

Section: Introductionmentioning

confidence: 99%

Immune mediators in the tumor microenvironment of prostate cancer

et al. 2017

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Prostate cancer tissue is composed of both cancer cells and host cells. The milieu of host components that compose the tumor is termed the tumor microenvironment (TME). Host cells can be those derived from the tissue in which the tumor originates (e.g., fibroblasts and endothelial cells) or those recruited, through chemotactic or other factors, to the tumor (e.g., circulating immune cells). Some immune cells are key players in the TME and represent a large proportion of non-tumor cells found within the tumor. Immune cells can have both anti-tumor and pro-tumor activity. In addition, crosstalk between prostate cancer cells and immune cells affects immune cell functions. In this review, we focus on immune cells and cytokines that contribute to tumor progression. We discuss T-regulatory and T helper 17 cells and macrophages as key modulators in prostate cancer progression. In addition, we discuss the roles of interleukin-6 and receptor activator of nuclear factor kappa-B ligand in modulating prostate cancer progression. This review highlights the concept that immune cells and cytokines offer a potentially promising target for prostate cancer therapy.

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Regulatory T cells: balancing protection versus pathology

Cited by 21 publications

References 76 publications

Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy

Clinical relevance of tumor infiltrating lymphocytes, PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy

Dawn of Monitoring Regulatory T Cells in (Pre-)clinical Studies: Their Relevance Is Slowly Recognised

Immune mediators in the tumor microenvironment of prostate cancer

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