The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Chemokine Expression in Melanoma Metastases Associated with CD8+ T-Cell Recruitment
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Abstract
Despite the frequent detection of circulating tumor antigen-specific T cells, either spontaneously or following active immunization or adoptive transfer, immune-mediated cancer regression occurs only in the minority of patients. One theoretical rate-limiting step is whether effector T cells successfully migrate into metastatic tumor sites. Affymetrix gene expression profiling done on a series of metastatic melanoma biopsies revealed a major segregation of samples based on the presence or absence of T-cell-associated transcripts. The presence of lymphocytes correlated with the expression of defined chemokine genes. A subset of six chemokines (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10) was confirmed by protein array and/or quantitative reverse transcription-PCR to be preferentially expressed in tumors that contained T cells. Corresponding chemokine receptors were found to be up-regulated on human CD8(+) effector T cells, and transwell migration assays confirmed the ability of each of these chemokines to promote migration of CD8(+) effector cells in vitro. Screening by chemokine protein array identified a subset of melanoma cell lines that produced a similar broad array of chemokines. These melanoma cells more effectively recruited human CD8(+) effector T cells when implanted as xenografts in nonobese diabetic/severe combined immunodeficient mice in vivo. Chemokine blockade with specific antibodies inhibited migration of CD8(+) T cells. Our results suggest that lack of critical chemokines in a subset of melanoma metastases may limit the migration of activated T cells, which in turn could limit the effectiveness of antitumor immunity.
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“Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on, treatment.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [6]
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“Tumor analysis from patients with metastatic melanoma receiving vaccine and cytokine therapies suggested a paradigm of two broad phenotypes characterized by the presence or absence a T cell-inflamed tumor.”
From Reimagining IDO Pathway Inhibition in Cancer Immunotherapy via Downstream Focus on the Tryptophan–Kynurenine–Aryl Hydrocarbon Axis (2019) · cites this paper as [6]
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“an effector population shown to be a target of downstream STING signaling involving the IFN-β-CXCL9/10 axis.54–58”
From Functional tumor cell-intrinsic STING, not host STING, drives local and systemic antitumor immunity and therapy efficacy following cryoablation (2023) · cites this paper as [55]
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Citations
Cites
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“The indicated chemokines are GRO (1), IL-8 (2 ), CTACK (3), CXCL16 (4 ), IP-10 (5), MCP-1 (6), MIG (7), MIP-1a (8), MIP-1h (9), PARC (10), and RANTES (11 ).”
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“Our results have implications for the use of autologous tumorinfiltrating lymphocytes (TIL) as an adoptive transfer immunotherapeutic strategy (23).”
ResultPriming of naive T cells inside tumors leads to eradication of established tumors
Yu, P., Lee, Y., Liu, W., Chin, R., Wang, J. H., Wang, Y., Schietinger, A., Philip, M., Schreiber, H. W., & Fu, Y. (2004) · Nature Immunology · doi:10.1038/ni1029 · Cited by 354 · cited 1×
“Transfection of tumor cells to express LIGHT results in potent tumor rejection (26), and introduction of an adenoviral vector encoding LIGHT can improve the control of preestablished tumors and promote rejection of micrometastases (27).”
BackgroundT cell costimulation by chemokine receptors
Molon, B., Gri, G., Bettella, M., Gómez‐Moutón, C., Lanzavecchia, A., Martínez‐A, C., Mañes, S., & Viola, A. (2005) · Nature Immunology · doi:10.1038/ni1191 · Cited by 343 · cited 1×
“Recent work has suggested that CXCR4 and CCR5 may cooperatively provide a costimulatory signal for T-cell activation (16) and that CCR5 on CD8 T cells may be important for the generation of a memory phenotype (17).”
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MethodEnhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A.
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“Clinical data have suggested an association between CXCR3 expression by peripheral T cells and favorable clinical outcome in stage III melanoma patients (28), arguing that the chemokine receptors expressed by T cells may be important in patients.”
BackgroundHarlin, H., Kuna, T. V., Peterson, A., Meng, Y., & Gajewski, T. F. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0118-2 · Cited by 144 · cited 1×
“Other studies have shown that the tumor-infiltrating lymphocyte population includes tumor antigen–specific T cells (21, 22), suggesting that this recruitment does include relevant cells.”
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“Transfection of tumor cells to express several chemokines before implantation in mice has shown improved tumor control in several models (24).”
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“Manipulation of Stat3 expression has indicated that down-regulation of Stat3 can result in increased expression of chemokine genes by tumor cells (20), suggesting that differential activity of a single oncogenic pathway may be capable of controlling the recruitment of inflammatory cells into the tumor vicinity.”
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Targeting the Primary Tumor to Generate CTL for the Effective Eradication of Spontaneous Metastases
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BackgroundThe Role of LIGHT in T Cell-Mediated Immunity
Wang, J., & Fu, Y. (2004) · Immunologic Research · doi:10.1385/ir:30:2:201 · Cited by 41 · cited 1×
“One attractive alternative is the tumor necrosis factor superfamily member LIGHT, which elicits chemokine expression from infiltrating stromal cells through engagement of the lymphotoxin hreceptor (25).”
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“There is some controversy in the literature on whether this chemokine attracts or repulses T cells (14, 15).”
BackgroundHuman tumour antigens recognized by T-cells: perspectives for new cancer vaccines
den Eynde, B. J. V., Gaugler, B., van der Bruggen, P., Coulie, P. G., Brichard, V. G., & Boon, T. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230681 · Cited by 20 · cited 1×
“The identification of defined epitopes derived from shared melanoma antigens presented by dominant HLA alleles has enabled the development of antigen-specific vaccination or adoptive T-cell therapy as strategies to increase the frequency of tumor-reactive effector T cells in an attempt to promote immunemediated reject…”
Background
Cited by
Sorted by citations
Elements of cancer immunity and the cancer–immune set point
Chen, D. S., & Mellman, I. (2017) · Nature · doi:10.1038/nature21349 · Cited by 5,352
Innate and adaptive immune cells in the tumor microenvironment
Gajewski, T. F., Schreiber, H., & Fu, Y.-X. (2013) · Nature Immunology · doi:10.1038/ni.2703 · Cited by 4,148
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788
“These data extend the observations of previous reports showing that CD8+ T lymphocytes and T cell active chemokines and T cell counterinhibitory molecules such as PD-1/PD-L1 and IDO1 are coregulated within tumors (4, 15, 21, 22) and confirm that response to anti–PD-1 blockade occurs primarily in patients with such a p…”
ResultApproaches to treat immune hot, altered and cold tumours with combination immunotherapies
Galon, J., & Bruni, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0007-y · Cited by 3,520
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
Spranger, S., Bao, R., & Gajewski, T. F. (2015) · Nature · doi:10.1038/nature14404 · Cited by 2,830
Self-citation
Metadata
- Authors
- Harlin, H., Meng, Y., Peterson, A. C., Zha, Y., Tretiakova, M., Slingluff, C., McKee, M., & Gajewski, T. F.
- Affiliations
- 1Department of Pathology,
- 2Department of Medicine, Section of Hematology/Oncology, and
- University of Virginia (US)
- University of Chicago (US)
- Venue
- Cancer Research
- Published
- 2009-04-01
- Volume
- 69
- Issue
- 7
- Pages
- 3077-3085
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC3886718
- OpenAlex
- W2162222767
- Cited by
- 1,121
- References
- 29
- Citations by year
- 2026: 40 · 2025: 58 · 2024: 89 · 2023: 95 · 2022: 118 · 2021: 121 · 2020: 105 · 2019: 87 · 2018: 69 · 2017: 77 · 2016: 51 · 2015: 42 · 2014: 29 · 2013: 37 · 2012: 28
- FWCI
- 17.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Burroughs Wellcome Fund
- University of Chicago
- National Cancer Institute (P01CA97296, R01 CA90575, R01CA090575, P01CA097296, P30CA044579)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- melanoma metastasis, chemokines, CD8+ T cell recruitment, T cell migration, MCP-1, CCL3, carbon tetrachloride, RANTES, CXCL9, CXCL10, chemokine receptors, tumor immune microenvironment, chemokine blockade, antitumor immunity, melanoma cell lines, xenografts
- MeSH terms
- Cell Movement, Multigene Family, Humans, Melanoma, Gene Expression, CD8-Positive T-Lymphocytes, Chemokines, Protein Array Analysis, Cell Line, Tumor
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