IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells
Abstract
Memory T cells in human non-small cell lung cancer are unresponsive to progressing tumors. T cells were evaluated at the single cell level by imaging the nuclear translocation of NF-kappaB and NFAT via immunofluorescence confocal microscopy as an early measure of responsiveness to T cell receptor triggering. Little translocation of NF-kappaB or NFAT occurred in tumor-associated T cells in response to CD3+CD28 cross-linking under conditions which led to maximal translocation in normal donor peripheral blood T cells. TNF-alpha induced maximal NF-kappaB translocation in these T cells, indicating that they remain receptive to alternative signaling pathways, and pulsing with IL-12 prior to TCR triggering reversed their apparent anergy. T cells from additional chronic inflammatory microenvironments demonstrated a similar refractoriness to TCR activation, suggesting either that a common regulatory mechanism present within the microenvironment controls these cells or that with continuous antigen exposure, they remain refractory to activation via the TCR.
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There is evidence of antigen-specific, T cell-intrinsic dysfunction in the tumor microenvironment.
“There is evidence indicating antigen specific, T cell-intrinsic dysfunction in the tumor microenvironment [15,16].”
From T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment (2013) · cites this paper as [16]
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T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
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Self-citation
- Authors
- Broderick, L., Brooks, S. P., Takita, H., Baer, A. N., Bernstein, J. M., & Bankert, R. B.
- Affiliations
- University at Buffalo, State University of New York (US)
- Kaleida Health (US)
- Corresponding author
- Bankert, Richard B.
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 118
- Issue
- 2-3
- Pages
- 159-169
- ISSN
- 1521-6616 (ISSN-L)
- OpenAlex
- W2080045946
- Cited by
- 47
- References
- 39
- Citations by year
- 2021: 2 · 2020: 1 · 2019: 1 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 1 · 2013: 4 · 2012: 4
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Cancer Institute (R01 CA 10897)
- National Institute of Allergy and Infectious Diseases (AI 07614, T32AI007614)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- IL-12, T cell anergy, memory T cells, non-small cell lung cancer, T cell receptor stimulation, NF-κB nuclear translocation, NFAT nuclear translocation, TNF-α, tumor microenvironment, chronic inflammation
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Cell Separation, Humans, Immunologic Memory, Lung Neoplasms, Lymph Nodes, Lymphocyte Activation, Receptors, Antigen, T-Cell, Tumor Necrosis Factor-alpha, Signal Transduction, T-Lymphocyte Subsets, Clonal Anergy, Microscopy, Confocal, Interleukin-12, Active Transport, Cell Nucleus
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