The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Characterization of Human Lung Tumor-Associated Fibroblasts and Their Ability to Modulate the Activation of Tumor-Associated T Cells
Open accessAbstract
The tumor microenvironment of human non-small cell lung cancer (NSCLC) is composed largely of stromal cells, including fibroblasts, yet these cells have been the focus of few studies. In this study, we established stromal cell cultures from primary NSCLC through isolation of adherent cells. Characterization of these cells by flow cytometry demonstrated a population which expressed a human fibroblast-specific 112-kDa surface molecule, Thy1, α-smooth muscle actin, and fibroblast activation protein, but failed to express CD45 and CD11b, a phenotype consistent with that of an activated myofibroblast. A subset of the tumor-associated fibroblasts (TAF) was found to express B7H1 (PD-L1) and B7DC (PD-L2) constitutively, and this expression was up-regulated by IFN-γ. Production of cytokines and chemokines, including IFN-γ, monokine induced by IFN-γ, IFN-γ-inducible protein-10, RANTES, and TGF-β1 was also demonstrated in these cells. Together, these characteristics provide multiple opportunities for the TAF to influence cellular interactions within the tumor microenvironment. To evaluate the ability of TAF to modulate tumor-associated T cell (TAT) activation, we conducted coculture experiments between autologous TAF and TAT. In five of eight tumors, TAF elicited a contact-dependent enhancement of TAT activation, even in the presence of a TGF-β1-mediated suppressive effect. In the three other tumors, TAF had a net suppressive effect upon TAT activation, and, in one of these cases, blockade of B7H1 or B7DC was able to completely abrogate the TAF-mediated suppression. We conclude that TAF in human NSCLC are functionally and phenotypically heterogeneous and provide multiple complex regulatory signals that have the potential to enhance or suppress TAT function in the tumor microenvironment.
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“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 [15]
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Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion
Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., Roche, P. C., Lu, J., Zhu, G., Tamada, K., et al. (2002) · Nature Medicine · doi:10.1038/nm730 · Cited by 5,025
Jemal, A., Murray, T., Ward, E., Samuels, A., Tiwari, R. C., Ghafoor, A., Feuer, E. J., & Thun, M. J. (2005) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.55.1.10 · Cited by 4,186
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Dong, H., Zhu, G., Tamada, K., & Chen, L. (1999) · Nature Medicine · doi:10.1038/70932 · Cited by 2,496
Inflammation. Basic principles and clinical correlates
(1989) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(89)90156-x · Cited by 2,388
Immunosuppressive networks in the tumour environment and their therapeutic relevance
Zou, W. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1586 · Cited by 2,057
Friends or foes — bipolar effects of the tumour stroma in cancer
Mueller, M. M., & Fusenig, N. E. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1477 · Cited by 1,817
Sharpe, A. H., & Freeman, G. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri727 · Cited by 1,759
Carcinoma-associated fibroblasts stimulate tumor progression of initiated human epithelium
Olumi, A., Grossfeld, G., Hayward, S., Carroll, P., Cunha, G., Hein, P., & Tlsty, T. (2000) · Breast Cancer Research · doi:10.1186/bcr138 · Cited by 1,463
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Research works printed but not linked: 70
- 2005, CA Cancer J. Clin., 10
- 2006, Clin. Immunol., 159
- 2005, Nat. Rev. Cancer, 263
- 2006, J. Immunol., 3082
- 2000, Hum. Gene Ther., 681
- 2001, Int. Immunol., 1147
- 2004, Nat. Rev. Immunol., 336
- 2003, Nat. Med., 562
- 2005, Cancer Res., 5020
- 2003, Cancer Res., 6478
- 2004, Immunity, 107
- 2006, Semin. Cancer Biol., 115
- 2001, Exp. Cell Res., 169
- 2004, Int. J. Cancer, 173
- 2001, Trends Immunol., 199
- 1998, J. Immunol., 1053
- 2005, Eur. J. Immunol., 2920
- 1997, Am. J. Pathol., 317
- 2000, Arthritis Res., 361
- 1999, Semin. Immunol., 3
- 1993, Nature, 70
- 2003, J. Immunol., 400
- 2005, J. Immunol., 898
- 1997, Cancer Res., 2937
- 1992, Int. J. Cancer, 621
- 2000, Nephrol. Dial. Transplant., 1766
- 2001, Biochem. Biophys. Res. Commun., 806
- 1989, Am. J. Respir. Cell Mol. Biol., 65
- 1992, Anat. Rec., 432
- 1994, Eur. Respir. J., 2131
- 1996, Cell. Immunol., 198
- 2002, Am. J. Physiol., C599
- 2001, Am. J. Pathol., 925
- 2006, Immunol. Invest., 297
- 2002, Nat. Rev. Immunol., 116
- 2004, Clin. Cancer Res., 5094
- 1999, Nat. Med., 1365
- 2001, Nat. Immunol., 261
- 2000, J. Exp. Med., 1027
- 2003, J. Immunol., 1257
- 2002, Nat. Med., 793
- 2003, Cancer Res., 7462
- 2003, Cancer Res., 6501
- 2001, Nat. Immunol., 123
- 2002, Acta Med. Okayama, 309
- 1991, J. Immunol., 1077
- 2003, J. Mol. Med., 281
- 2002, J. Immunol., 3581
- 2002, J. Immunol., 5538
- 2002, Immunol. Lett., 57
- 2001, J. Exp. Med., 839
- 2003, J. Exp. Med., 31
- 2004, Nat. Rev. Cancer, 839
- 2003, Am. J. Pathol., 1291
- 2002, Trends Immunol., 144
- 2000, Cytokine, 368
- 2000, Am. J. Respir. Crit. Care Med., 1466
- 2003, J. Interferon Cytokine Res., 591
- 2000, Hum. Gene Ther., 247
- 1996, J. Exp. Med., 981
- 1973, Science, 1057
- 1975, J. Natl. Cancer Inst., 913
- 1977, Cancer Res., 2544
- 1996, Physiol. Rev., 69
- 1999, Cancer Res., 5002
- 2001, Cancer Res., 8135
- 1990, Proc. Natl. Acad. Sci. USA, 75
- 1986, Cancer Res., 3290
- 1991, Cancer Res., 3753
- 2004, Lung Cancer, S163
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Items 101–102 of 102
Chivu-Economescu, M., Necula, L. G., Matei, L., Dragu, D., Bleotu, C., Sorop, A., Herlea, V., Dima, S., Popescu, I., & Diaconu, C. C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063214 · Cited by 42
Herrera-Campos, A. B., Zamudio-Martinez, E., Delgado-Bellido, D., Fernández-Cortés, M., Montuenga, L. M., Oliver, F. J., & Garcia-Diaz, A. (2022) · Cancers · doi:10.3390/cancers14112740 · Cited by 17
Metadata
- Authors
- Nazareth, M. R., Broderick, L., Simpson-Abelson, M. R., Kelleher, R. J., Yokota, S. J., & Bankert, R. B.
- Affiliations
- University at Buffalo, State University of New York (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-01
- Volume
- 178
- Issue
- 9
- Pages
- 5552-5562
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2105055793
- Cited by
- 259
- References
- 72
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 21 · 2023: 16 · 2022: 24 · 2021: 25 · 2020: 21 · 2019: 20 · 2018: 20 · 2017: 10 · 2016: 14 · 2015: 10 · 2014: 13 · 2013: 8 · 2012: 8
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- John R. Oishei Foundation
- U.S. Public Health Service
- National Cancer Institute (R01 CA 10897)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- cancer-associated fibroblasts, non-small cell lung cancer, tumor microenvironment, tumor-associated T cells, T cell activation, PD-L1, PD-L2, myofibroblasts, interferon-gamma, TGF-β1, cytokine and chemokine production, stromal cells, immunosuppression, contact-dependent suppression
- MeSH terms
- Carcinoma, Non-Small-Cell Lung, Fibroblasts, Humans, Interferon-gamma, Lung Neoplasms, Lymphocyte Activation, Receptors, Antigen, T-Cell, T-Lymphocytes, Tumor Cells, Cultured, Biomarkers, Tumor, Antigens, CD, Cytokines, Transforming Growth Factor beta, B7-1 Antigen, Coculture Techniques, Chemokines, B7-H1 Antigen, Programmed Cell Death 1 Ligand 2 Protein
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