Distinct Role for CD8 T Cells toward Cutaneous Tumors and Visceral Metastases
Open accessAbstract
The growth of immunogenic tumors in immunocompetent individuals is one of the oldest conundrums in tumor immunology. Although the ability of mouse CD8+ T cells to control transplanted tumors is well documented, little is known about their impact on autochthonous tumors. To gain insight into the role of CD8+ T cells during the course of cancer development, we produced a novel model of spontaneous melanoma. The metallothionein (MT)-ret/AAD mouse is transgenic for the RET oncogene and the chimeric MHC molecule AAD (α1-α2 domains of HLA-A2 linked to α3 domain of H2-Dd). This model recapitulates the natural history of human melanoma, and expression of the AAD molecule makes it suitable for analyzing CD8+ T cell responses directed against peptide Ags that have been previously identified in HLA-A2+ melanoma patients. We found that, as tumors grow, mice develop a broad melanoma-specific CD8+ T cell response. Occurrence of cutaneous nodules is not affected by CD8+ T cell depletion, showing that although CD8+ T cells are functional, they have no effect on established cutaneous tumors. However, depleted mice die from visceral disease much earlier than controls, showing that CD8+ T cells control metastasis spreading and disease progression. Antigenic modulation is observed in visceral metastases, suggesting that visceral nodules may be subject to immunoediting. Our data demonstrate that growth of melanoma in the MT-ret/AAD model involves several tolerance mechanisms sequentially. They also reveal a different role for CD8+ T cells toward early stage of cutaneous tumors and late visceral metastatic stage of the disease.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a spontaneous mouse melanoma model, dormancy in micrometastatic lesions is mediated by immunosurveillance.
“studies in a spontaneous mouse melanoma model suggest that dormancy in micrometastatic lesions is mediated by immunosurveillance 131,132”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [131]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cancer immunoediting: from immunosurveillance to tumor escape
Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., & Schreiber, R. D. (2002) · Nature Immunology · doi:10.1038/ni1102-991 · Cited by 5,393 · see citing works
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 · see citing works
Cancer immunotherapy: moving beyond current vaccines
Rosenberg, S. A., Yang, J. C.-H., & Restifo, N. P. (2004) · Nature Medicine · doi:10.1038/nm1100 · Cited by 2,956 · see citing works
Balch, C. M., Soong, S., Gershenwald, J. E., Thompson, J. F., Reintgen, D. S., Cascinelli, N., Urist, M. M., McMasters, K. M., Ross, M. I., Kirkwood, J. M., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.16.3622 · Cited by 2,385 · see citing works
Regulatory T cells, tumour immunity and immunotherapy
Zou, W. (2006) · Nature reviews. Immunology · doi:10.1038/nri1806 · Cited by 2,075 · see citing works
Thurner, B., Haendle, I., Röder, C., Dieckmann, D., Keikavoussi, P., Jonuleit, H., Bender, A., Maczek, C., Schreiner, D., Driesch, P. V. D., et al. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.11.1669 · Cited by 1,226 · see citing works
Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients
Lee, P. P., Yee, C., Savage, P. A., Fong, L. H., Brockstedt, D. G., Weber, J. S., Johnson, D. L., Swetter, S. M., Thompson, J. A., Greenberg, P. D., et al. (1999) · Nature Medicine · doi:10.1038/9525 · Cited by 1,117 · see citing works
Woo, E. Y., Chu, C., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., Rubin, S. C., Kaiser, L. R., & June, C. H. (2001) · PubMed · Cited by 1,113 · see citing works
Natural selection of tumor variants in the generation of “tumor escape” phenotypes
Khong, H. T., & Restifo, N. P. (2002) · Nature Immunology · doi:10.1038/ni1102-999 · Cited by 1,058 · see citing works
Smyth, M. J., Dunn, G. P., & Schreiber, R. D. (2006) · Advances in immunology · doi:10.1016/s0065-2776(06)90001-7 · Cited by 872 · see citing works
Banchereau, J., Palucka, A. K., Dhodapkar, M. V., Burkeholder, S. B., Taquet, N., Rolland, A., Taquet, S., Coquery, S., Wittkowski, K. M., Bhardwaj, N., et al. (2001) · PubMed · Cited by 809 · see citing works
Ghiringhelli, F., Puig, P. E., Roux, S., Parcellier, A., Schmitt, E., Solary, É., Kroemer, G., Martin, F., Chauffert, B., & Zitvogel, L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050463 · Cited by 776 · see citing works
Serafini, P., Borrello, I., & Bronte, V. (2005) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2005.07.005 · Cited by 758 · see citing works
Viguier, M. A., Lemaı̂tre, F., VEROLA, O., Cho, M.-S., Gorochov, G., Dubertret, L., Bachelez, H., Kourilsky, P., & Ferradini, L. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.2.1444 · Cited by 686 · see citing works
HUMAN T CELL RESPONSES AGAINST MELANOMA
Boon, T., Coulie, P. G., den Eynde, B. J. V., & van der Bruggen, P. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.24.021605.090733 · Cited by 651 · see citing works
Checkpoint Blockade in Cancer Immunotherapy
Korman, A. J., Peggs, K. S., & Allison, J. P. (2006) · Advances in immunology · doi:10.1016/s0065-2776(06)90008-x · Cited by 577 · see citing works
Rosenberg, S. A., Sherry, R. M., Morton, K. E., Sharfman, W., Yang, J. C., Topalian, S. L., Royal, R. E., Kammula, U. S., Restifo, N. P., Hughes, M. S., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.9.6169 · Cited by 460 · see citing works
Immune surveillance against a solid tumor fails because of immunological ignorance
Ochsenbein, A. F., Klenerman, P., Karrer, U. W., Ludewig, B., Pericin, M., Hengartner, H., & Zinkernagel, R. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2233 · Cited by 453 · see citing works
Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance
Willimsky, G., & Blankenstein, T. J. F. (2005) · Nature · doi:10.1038/nature03954 · Cited by 439 · see citing works
Zippelius, A., Batard, P., Rubio‐Godoy, V., Bioley, G., Líénard, D., Lejeune, F. J., Rimoldi, D., Guillaume, P., Meidenbauer, N., Mackensen, A., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3066 · Cited by 361 · see citing works
Germeau, C., Ma, W., Schiavetti, F., Lurquin, C., Henry, E., Vigneron, N., Brasseur, F., Lethé, B., Plaen, E. D., Velu, T. J., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20041379 · Cited by 232 · see citing works
Transgenic mouse model for skin malignant melanoma
Kato, M., Takahashi, M., Akhand, A. A., Liu, W., Dai, Y. M., Shimizu, S., Iwamoto, T., Suzuki, H., & Nakashima, I. (1998) · Oncogene · doi:10.1038/sj.onc.1202077 · Cited by 220 · see citing works
Self-citationCoulie, P. G., Karanikas, V., Colau, D., Lurquin, C., Landry, C., Marchand, M., Dorval, T., Brichard, V. G., & Boon, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161260098 · Cited by 220 · see citing works
Mortarini, R., Piris, A., Maurichi, A., Molla, A., Bersani, I., Bono, A. V., Bartoli, C., Santinami, M., Lombardo, C., Ravagnani, F., et al. (2003) · PubMed · Cited by 177 · see citing works
Direct evidence to support the immunosurveillance concept in a human regressive melanoma.
Mackensen, A., Carcelain, G., Viel, S., Raynal, M. C., Michalaki, H., Triebel, F., Bosq, J., & Hercend, T. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117116 · Cited by 165 · see citing works
Physiopathology and genetics of vitiligo
Passeron, T., & Ortonne, J. (2005) · Journal of Autoimmunity · doi:10.1016/j.jaut.2005.10.001 · Cited by 162 · see citing works
Cutaneous melanoma: available therapy for metastatic disease
Tarhini, A. A., & Agarwala, S. S. (2006) · Dermatologic Therapy · doi:10.1111/j.1529-8019.2005.00052.x · Cited by 146 · see citing works
Harlin, H., Kuna, T. V., Peterson, A., Meng, Y., & Gajewski, T. F. (2006) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-005-0118-2 · Cited by 143 · see citing works
Dworacki, G., Meidenbauer, N., Kuss, I., Hoffmann, T. K., Gooding, W. E., Lotze, M. T., & Whiteside, T. L. (2001) · PubMed · Cited by 129 · see citing works
Nakagomi, H., Pisa, P., Pisa, E. K., et al. (1995) · International Journal of Cancer · doi:10.1002/ijc.2910630311 · Cited by 129 · see citing works
Mackensen, A., Ferradini, L., Carcelain, G., Triebel, F., Faure, F., Viel, S., & Hercend, T. (1993) · PubMed · Cited by 118 · see citing works
Direct Evidence to Support the Role of Antigen-Specific CD8+ T Cells in Melanoma-Associated Vitiligo
Gal, F. L., Lefebvre, P. P., Deschemin, J., et al. (2001) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2001.01605.x · Cited by 110 · see citing works
den Hove, L. E. V., Gool, S. W. V., Poppel, H. V., et al. (1997) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1997.4771375.x · Cited by 102 · see citing works
Identifying and Overcoming Immune Resistance Mechanisms in the Melanoma Tumor Microenvironment
Gajewski, T. F. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2517 · Cited by 97 · see citing works
Importance of MHC class 1 α2 and α3 domains in the recognition of self and non-self MHC molecules
Newberg, M. H., Smith, D. H., Haertel, S. B., et al. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.7.2473 · Cited by 93 · see citing works
Sanchez-Perez, L. A., Kottke, T. J., Díaz, R. M., Ahmed, A. U., Thompson, J., Chong, H., Melcher, A. A., Holmen, S. L., Daniels, G. A., & Vile, R. G. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3216 · Cited by 86 · see citing works
Whiteside, T. L. (2002) · Vaccine · doi:10.1016/s0264-410x(02)00387-0 · Cited by 73 · see citing works
Meidenbauer, N., Zippelius, A., Pittet, M. J., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-1341 · Cited by 59 · see citing works
Spontaneous Vitiligo in an Animal Model for Human Melanoma
Lengagne, R., Gal, F. L., Garcette, M., Fiette, L., Avé, P., Kato, M., Briand, J., Massot, C., Nakashima, I., Rénia, L., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-2828 · Cited by 57 · see citing works
Self-citationSensi, M., Farina, C., Maccalli, C., et al. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119215 · Cited by 57 · see citing works
Mullins, D. W., Bullock, T. N. J., Colella, T. A., et al. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.9.4853 · Cited by 55 · see citing works
Human tumor-specific T lymphocytes: does function matter more than number?
Coulie, P. G., & Connerotte, T. (2005) · Current Opinion in Immunology · doi:10.1016/j.coi.2005.03.002 · Cited by 50 · see citing works
Liu, K., Caldwell, S. A., & Abrams, S. I. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4269 · Cited by 38 · see citing works
Gal, F. L., Prévost‐Blondel, A., Lengagne, R., et al. (2001) · International Journal of Cancer · doi:10.1002/ijc.10186 · Cited by 32 · see citing works
Self-citationRET tyrosine kinase enhances hair growth in association with promotion of melanogenesis
Kato, M., Takeda, K., Kawamoto, Y., Tsuzuki, T., Dai, Y., Nakayama, S., Toriyama, K., Tamada, Y., Takahashi, M., & Nakashima, I. (2001) · Oncogene · doi:10.1038/sj.onc.1204918 · Cited by 30 · see citing works
Self-citationMurine models of malignant melanoma
Tietze, M. K., & Chin, L. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01781-0 · Cited by 24 · see citing works
Mackensen, A., Ferradini, L., Carcelain, G., et al. (1993) · Melanoma Research · doi:10.1097/00008390-199309002-00106 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Eyles, J., Puaux, A.-L., Wang, X., Toh, B., Prakash, C., Hong, M., Tan, T. G., Zheng, L., Ong, L. C., Jin, Y., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42002 · Cited by 506 · see citing works
Self-citationInside and out: the activities of senescence in cancer
Pérez-Mancera, P. A., Young, A. R. J., & Narita, M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3773 · Cited by 462 · see citing works
PTEN functions as a melanoma tumor suppressor by promoting host immune response
Dong, Y., Richards, J.-A., Gupta, R., Aung, P. P., Emley, A., Kluger, Y., Dogra, S. K., Mahalingam, M., & Wajapeyee, N. (2014) · Oncogene · doi:10.1038/onc.2013.409 · Cited by 113 · see citing works
Chapon, M., Randriamampita, C., Maubec, E., Badoual, C., Fouquet, S., Wang, S.-F., Marinho, E., Farhi, D., Garcette, M., Jacobelli, S., et al. (2011) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.30 · Cited by 86 · see citing works
Self-citation
- Authors
- Lengagne, R., Graff-Dubois, S., Garcette, M., Renia, L., Kato, M., Guillet, J.-G., Engelhard, V. H., Avril, M.-F., Abastado, J.-P., & Prévost-Blondel, A.
- Affiliations
- Institut Cochin, Université Paris Descartes, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8104 , Paris ,
- Chubu University (JP)
- Carter Immunology Center and Department of Microbiology, University of Virginia School of Medicine , Charlottesville, VA 22908
- Centre National de la Recherche Scientifique (FR)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-01-01
- Volume
- 180
- Issue
- 1
- Pages
- 130-137
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1863467599
- Cited by
- 64
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 7 · 2014: 6 · 2013: 5 · 2012: 3
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Association pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- U.S. Public Health Service (CA78400)
- National Cancer Institute (CA78400, R01CA078400)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- CD8+ T cells, melanoma, RET oncogene, cutaneous tumors, visceral metastases, immunoediting, antigenic modulation, T cell tolerance, tumor immunology, autochthonous tumors, HLA-A2
- MeSH terms
- Animals, Disease Models, Animal, HLA Antigens, Humans, Lymphocyte Depletion, Melanoma, Mice, Transgenic, Neoplasm Metastasis, Skin Neoplasms, Viscera, HLA-A2 Antigen, CD8-Positive T-Lymphocytes, Tumor Escape, Proto-Oncogene Proteins c-ret, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
