335 research outputs found
Abstract 4932: Oxygen sensing by T cells establishes an immunologically favorable metastatic niche
No full textAbstract
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function. Tumor colonization is accompanied by PHD-protein-dependent induction of pulmonary Treg cells and suppression of IFN-γ-dependent tumor clearance. T-cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: David Clever, Nicholas Restifo. Oxygen sensing by T cells establishes an immunologically favorable metastatic niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4932. doi:10.1158/1538-7445.AM2017-4932</jats:p
A GENOME-SCALE CRISPR SCREEN TO IDENTIFY ESSENTIAL GENES FOR THE EFFECTOR FUNCTION OF CYTOTOXIC T LYMPHOCYTES
No full textPh.D.Somatic gene mutations and dysregulations can alter the vulnerability of a cancer cell to T cell based immune selection. To systematically identify genes that positively regulate the sensitivity of cancer cells to T cell-mediated cytolysis, we developed a two cell-type (2CT) functional screening platform by combining human T cell engineering and CRISPR (Clustered regularly interspaced short palindromic repeats) genome editing. Using the 2CT genome-scale perturbation screen in melanoma cells, we identified and validated multiple genes whose loss impaired the effector function of T cells. Moreover, we uncover a group of genes from these screens that correlates with cytolytic activity across the majority of the cancer types, reflecting context independence of these genes in the modulation of inherent T cell responses in multiple cancers. This study demonstrates the broad applicability of 2CT CRISPR screens to study the interaction of cancer cells with immune cells and identify novel therapeutic targets for cellular therapies
Vaccines against virally induced cancers, Ciba Foundation Symposium 187 edited by D.J. Chadwick and J. Marsh, John Wiley & Sons; Chichester 1995, xi + 281 pp. £ 47.50. ISBN 0 471 95026 2
No full textCan Antitumor Immunity Help to Explain “Oncogene Addiction”?
No full text“Oncogene addiction” refers to the process of tumor cell death that can occur after inactivation of a single oncogene. In this issue of Cancer Cell, Rakhra et al. argue that complete tumor clearance after molecular targeted therapies requires a functioning immune system, pointing the way toward radically new combination therapies
Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells
No full textThe T cell compartment is phenotypically and functionally heterogeneous; subsets of naive and memory cells have different functional properties, and also differ with respect to homeostatic potential and the ability to persist in vivo. Human stem cell memory T (TSCM) cells, which possess superior immune reconstitution and antitumor response capabilities, can be identified by polychromatic flow cytometry on the basis of the simultaneous expression of several naive markers together with the memory marker CD95. We describe here a protocol based on the minimum set of markers required for optimal identification of human and nonhuman primate (NHP) TSCM cells with commonly available flow cytometers. By using flow sorters, TSCM cells can thereby be isolated efficiently at high yield and purity. With the use of the 5.5-h isolation procedure, depending on the number of cells needed, the sorting procedure can last for 2-15 h. We also indicate multiple strategies for their efficient expansion in vitro at consistent numbers for functional characterization or adoptive transfer experiments
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