Dataset Information

Adoptive Cell Therapy in Treating Pediatric Solid Tumors.

ABSTRACT: PURPOSE OF REVIEW:This review will discuss the challenges facing adoptive cell techniques in the treatment of solid tumors and examine the therapies that are in development for specifically pediatric solid tumors. RECENT FINDINGS:Targeting solid tumors with adoptive cell therapy has been limited by the inhibitory tumor microenvironment and heterogeneous expression of targetable antigens. Many creative strategies to overcome these limitations are being developed but still need to be tested clinically. Early phase clinical trials in neuroblastoma with GD2 CAR T cells are promising but results need to be validated on a larger scale. Most research in other pediatric solid tumors is still in early stages. Adoptive cell therapy represents a useful tool to improve the outcomes of many pediatric solid tumors but significant study is still required. Several clinical trials are ongoing to test therapies that have shown promise in the lab.

SUBMITTER: Tesfaye M

PROVIDER: S-EPMC6386156 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adoptive Cell Therapy in Treating Pediatric Solid Tumors.

Tesfaye Mekdem M Savoldo Barbara B

Current oncology reports 20180801 9

<h4>Purpose of review</h4>This review will discuss the challenges facing adoptive cell techniques in the treatment of solid tumors and examine the therapies that are in development for specifically pediatric solid tumors.<h4>Recent findings</h4>Targeting solid tumors with adoptive cell therapy has been limited by the inhibitory tumor microenvironment and heterogeneous expression of targetable antigens. Many creative strategies to overcome these limitations are being developed but still need to b ...[more]

PMID: 30069644

Similar Datasets

Project description:Tumor-reactive CD8 T cells found in cancer patients are frequently dysfunctional, unable to halt tumor growth. Adoptive T cell transfer (ACT), the administration of large numbers of in vitro-generated cytolytic tumor-reactive CD8 T cells, is an important cancer immune therapy being pursued. However, a limitation of ACT is that transferred CD8 T cells often rapidly lose effector function, and despite exciting results in certain malignancies, few ACT clinical trials have shown responses in solid tumors. Here, we developed preclinical cancer mouse models to investigate if and how tumor-specific CD4 T cells can be enlisted to overcome CD8 T cell dysfunction in the setting of ACT. In situ confocal microscopy of color-coded cancer cells, tumor-specific CD8 and CD4 T cells, and antigen presenting cells (APC), combined with functional studies, revealed that the spatial positioning and interactions of CD8 and CD4 T cells, but not their numbers, dictates ACT efficacy and anti-tumor responses. We uncover a new role of antigen-specific CD4 T cells in addition to the known requirement for CD4 T cells during priming/activation of naïve CD8 T cells. CD4 T cells must co-engage with CD8 T cells and APC cross-presenting CD8- and CD4-tumor antigens during the effector phase, forming a three-cell-cluster (triad), to license CD8 T cell cytotoxicity and mediate cancer cell elimination. Triad formation transcriptionally and epigenetically reprogram CD8 T cells, prevent T cell dysfunction/exhaustion, and ultimately lead to the elimination of large established tumors and confer long-term protection from recurrence. When intratumoral triad formation was disrupted, adoptively transferred CD8 T cells could not be reprogrammed, and tumors progressed despite equal numbers of tumor-infiltrating CD8 and CD4 T cells. Strikingly, the formation of CD4 T cell::CD8 T cell::APC triads in tumors of patients with lung cancers treated with immune checkpoint blockade was associated with clinical responses, but not CD4::APC dyads or overall numbers of CD8 or CD4 T cells, demonstrating the importance of triads in non-ACT settings in humans. Our work uncovers intratumoral triads as a key requirement for anti-tumor immunity and a new role for CD4 T cells in CD8 T cell cytotoxicity and cancer cell eradication.

Dataset Information

Adoptive Cell Therapy in Treating Pediatric Solid Tumors.

Publications

Adoptive Cell Therapy in Treating Pediatric Solid Tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets