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Summary: Regulatory T cells (Tregs) have enormous therapeutic potential to treat a variety of immunopathologies characterized by aberrant immune activation. Adoptive transfer of ex vivo expanded autologous Tregs continues to progress through mid- to late-phase clinical trials in several disease spaces and has generated promising preliminary safety and efficacy signals to date. However, the practicalities of this strategy outside of the clinical trial setting remain challenging. Here, we review the current landscape of regulatory T-cell therapy, considering emergent approaches and technologies presenting novel ways to engage Tregs, and reflect on the progress necessary to deliver their therapeutic potential to patients. Regulatory T cells (Tregs) have enormous therapeutic potential to treat a variety of immunopathologies characterized by aberrant immune activation. However, the practicalities of Treg cell therapy outside of the clinical trial setting remain challenging. Here, we review the current landscape of Treg cell therapy, considering emergent approaches and technologies presenting novel ways to engage Tregs, and reflect on the progress necessary to deliver their therapeutic capabilities to patients. [ABSTRACT FROM AUTHOR]

Radiation therapy has the potential to modulate the immune system in a variety of ways, and given the critical role of the immune system in cancer elimination, it is becoming increasingly important to understand how radiation can be strategically implemented in conjunction with approved immunotherapies to improve the cancer patient's chance of cure and/or quality of life. Current successful, approved cancer immunotherapies fall into two broad classes: antibodies and cellular therapies. Approved cellular therapies thus far consist of Chimeric Antigen Receptor (CAR) T-cells targeting CD19 for refractory non-Hodgkin lymphoma and relapsed or refractory acute lymphoblastic leukemia. Part of the ardor surrounding CAR T-cells stems from the fact that the survival curve of treated patients has a clear plateau, meaning that a number of patients with aggressive, disseminated disease who would have otherwise died rather rapidly appear to now be cured, commonly after just one dose. Despite an encouraging number of these durable remissions, the majority do still relapse. In this review, we discuss the potential for strategically utilizing radiation to further improve CAR T-cell patient outcomes. Given that there are currently over 750 cellular therapies in development, half of which are now in clinical trial, CAR T-cell usage will inevitably expand; as the field grows in importance and effectiveness, radiation oncology has the opportunity to coevolve symbiotically and steer these novel, exciting live therapies to new depths. [ABSTRACT FROM AUTHOR]

Innovative immunotherapies based on immune checkpoint targeting antibodies and engineered T cells are transforming the way we approach cancer treatment. However, although these T cell centered strategies result in marked and durable responses in patients across many different tumor types, they provide therapeutic efficacy only in a proportion of patients. A major challenge of immuno‐oncology is thereby to identify mechanisms responsible for resistance to cancer immunotherapy in order to overcome them via adapted strategies that will ultimately improve intrinsic efficacy and response rates. Here, we focus on the barriers that restrain the trafficking of chimeric antigen receptor (CAR)‐expressing T cells to solid tumors. Upon infusion, CAR T cells need to home into malignant sites, navigate within complex tumor environments, form productive interactions with cancer cells, deliver their cytotoxic activities, and finally persist. We review the accumulating evidence that the microenvironment of solid tumors contains multiple obstacles that hinder CAR T cells in the dynamic steps underlying their trafficking. We focus on how these hurdles may in part account for the failure of CAR T cell clinical trials in human carcinomas. Given the engineered nature of CAR T cells and possibilities to modify the tumor environment, there are ample opportunities to augment CAR T cell ability to efficiently find and combat tumors. We present some of these strategies, which represent a dynamic field of research with high potential for clinical applicability. [ABSTRACT FROM AUTHOR]

Many cancers are predominantly diagnosed in older individuals and chronic inflammation has a major impact on the overall health and immune function of older cancer patients. Chronic inflammation is a feature of aging, it can accelerate disease in many cancers and it is often exacerbated during conventional treatments for cancer. This review will provide an overview of the factors that lead to increased inflammation in older individuals and/or individuals with cancer, as well as those that result from conventional treatments for cancer, using ovarian cancer (OC) and multiple myeloma (MM) as key examples. We will also consider the impact of chronic inflammation on immune function, with a particular focus on T cells as they are key targets for novel cancer immunotherapies. Overall, this review aims to highlight specific pathways for potential interventions that may be able to mitigate the impact of chronic inflammation in older cancer patients. [ABSTRACT FROM AUTHOR]