Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

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Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.

/pdf/regulatory-t-cells-in-tumor-microenvironment-new-mechanisms-4c8dmp49vz.pdf

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes the iterative nature of the response where the killing of tumor cells by T cells initiates subsequent rounds of antigen presentation and T cell stimulation, maintaining active immunity and adapting it to tumor evolution. Any step of the cycle can become rate-limiting, rendering the immune system unable to control tumor growth. Here, we update the cancer-immunity cycle based on the remarkable progress of the past decade. Understanding the mechanism of checkpoint inhibition has evolved, as has our view of dendritic cells in sustaining anti-tumor immunity. We additionally account for the role of the tumor microenvironment in facilitating, not just suppressing, the anti-cancer response, and discuss the importance of considering a tumor’s immunological phenotype, the “immunotype”. While these new insights add some complexity to the cycle, they also provide new targets for research and therapeutic intervention. 

The cancer-immunity cycle: Indication, genotype, and immunotype.

Background: Regulatory T cells (Tregs), traditionally recognized as potent suppressors of immune response, are increasingly attracting attention because of a second major function: residing in pare...

A Unique Population of Regulatory T Cells in Heart Potentiates Cardiac Protection From Myocardial Infarction.

Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF

Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells

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Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF

Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells