Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

Banerjee, Hridesh; Nieves-Rosado, Hector M; Kulkarni, Aditi; Murter, Benjamin; McGrath, Kyle; Chandran, Uma; Chang, Alexander; Szymczak-Workman, Andrea L.; Vujanović, Lazar; Delgoffe, Greg M.; Ferris, Robert L.; Kane, Lawrence P.

doi:10.1016/j.celrep.2021.109699

Cited by 55 publications

(37 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This may explain our results, in which activation of CD8 + T cells, as well as the high abundance of memory T cells, significantly prolongs the OS time of CC patients. Surprisingly, the results showed that high Treg infiltration was significantly associated with good prognosis of patients, which was quite opposite to the phenomenon widely reported thus far ( Banerjee et al, 2021 ; Dahlhoff et al, 2021 ; Peng et al, 2021 ). In previous reports, little literature has mentioned that Treg can participate in the immune process as a protective factor.…”

Section: Discussioncontrasting

confidence: 98%

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Wang

Ding

Cui

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.

show abstract

Section: Discussioncontrasting

confidence: 98%

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Wang

Ding

Cui

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…TIM-3 is expressed on fully differentiated Th1 cells and activated by binding to its ligand galectin-9 [137]. This leads to termination of Th1-driven immunity and an increased Tregs suppressive activity [137][138][139]. In cervical cancer, various immune checkpoints were often co-expressed on effector T cells and elevated upon metastatic involvement in TDLN [140], observations consistent with the acquisition of an exhausted phenotype.…”

Section: T-cell Activation and Inhibitionmentioning

confidence: 74%

Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis

Rafael

Rotman

Brouwer

et al. 2022

JCM

View full text Add to dashboard Cite

Human papillomavirus (HPV) infection drives tumorigenesis in almost all cervical cancers and a fraction of vulvar and penile cancers. Due to increasing incidence and low vaccination rates, many will still have to face HPV-related morbidity and mortality in the upcoming years. Current treatment options (i.e., surgery and/or chemoradiation) for urogenital (pre-)malignancies can have profound psychosocial and psychosexual effects on patients. Moreover, in the setting of advanced disease, responses to current therapies remain poor and nondurable, highlighting the unmet need for novel therapies that prevent recurrent disease and improve clinical outcome. Immunotherapy can be a useful addition to the current therapeutic strategies in various settings of disease, offering relatively fewer adverse effects and potential improvement in survival. This review discusses immune evasion mechanisms accompanying HPV infection and HPV-related tumorigenesis and summarizes current immunotherapeutic approaches for the treatment of HPV-related (pre-)malignant lesions of the uterine cervix, vulva, and penis.

show abstract

“…TIM-3+ Treg cells have been associated with multiple cancers including CRC and have a role in regulating immune responses by driving T cell inhibition or exhaustion. They express CD39/CD73 (Figure 1F), IL-10, and TGF-b (Figure 1D) and upregulate the expression of checkpoint receptors (Figure 1G), such as CTLA-4, PD-1, and LAG-3 (166)(167)(168)(169)(170). CRC tumors implanted in TIM-3 deficient mice have a reduced infiltration of Treg cells, reduced CD8+ Teff cell exhaustion, and slower tumor growth (170).…”

Section: Tumor-infiltrating Treg Cells and Crcmentioning

confidence: 99%

Colorectal Cancer-Infiltrating Regulatory T Cells: Functional Heterogeneity, Metabolic Adaptation, and Therapeutic Targeting

2022

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a heterogeneous disease with one of the highest rates of incidence and mortality among cancers worldwide. Understanding the CRC tumor microenvironment (TME) is essential to improve diagnosis and treatment. Within the CRC TME, tumor-infiltrating lymphocytes (TILs) consist of a heterogeneous mixture of adaptive immune cells composed of mainly anti-tumor effector T cells (CD4+ and CD8+ subpopulations), and suppressive regulatory CD4+ T (Treg) cells. The balance between these two populations is critical in anti-tumor immunity. In general, while tumor antigen-specific T cell responses are observed, tumor clearance frequently does not occur. Treg cells are considered to play an important role in tumor immune escape by hampering effective anti-tumor immune responses. Therefore, CRC-tumors with increased numbers of Treg cells have been associated with promoting tumor development, immunotherapy failure, and a poorer prognosis. Enrichment of Treg cells in CRC can have multiple causes including their differentiation, recruitment, and preferential transcriptional and metabolic adaptation to the TME. Targeting tumor-associated Treg cell may be an effective addition to current immunotherapy approaches. Strategies for depleting Treg cells, such as low-dose cyclophosphamide treatment, or targeting one or more checkpoint receptors such as CTLA-4 with PD-1 with monoclonal antibodies, have been explored. These have resulted in activation of anti-tumor immune responses in CRC-patients. Overall, it seems likely that CRC-associated Treg cells play an important role in determining the success of such therapeutic approaches. Here, we review our understanding of the role of Treg cells in CRC, the possible mechanisms that support their homeostasis in the tumor microenvironment, and current approaches for manipulating Treg cells function in cancer.

show abstract

Expression of Tim-3 drives phenotypic and functional changes in Treg cells in secondary lymphoid organs and the tumor microenvironment

Cited by 55 publications

References 65 publications

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Fanconi Anemia Pathway Genes Advance Cervical Cancer via Immune Regulation and Cell Adhesion

Immunotherapeutic Approaches for the Treatment of HPV-Associated (Pre-)Cancer of the Cervix, Vulva and Penis

Colorectal Cancer-Infiltrating Regulatory T Cells: Functional Heterogeneity, Metabolic Adaptation, and Therapeutic Targeting

Contact Info

Product

Resources

About