Cited by 940Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

The DOI matches its Crossref record; 93 of the 93 references it cites were found in a registry or an index.

CTLA-4: new insights into its biological function and use in tumor immunotherapy

Egen, Jackson G., Kuhns, Michael S., Allison, James P.·2002·Nature Immunology

Open this paper in CoChat — free account

Abstract

The discovery of multiple costimulatory cell surface molecules that influence the course of T cell activation has increased our appreciation of the complexity of the T cell response. It remains clear, however, that CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) are the critical costimulatory receptors that determine the early outcome of stimulation through the T cell antigen receptor (TCR). Details of how the T cell integrates TCR stimulation with the costimulatory signals of CD28 and the inhibitory signals of CTLA-4 remain to be established, but unique features of the cell biology of CTLA-4 provide important insights into its function. We summarize here recent findings that suggest a previously unrecognized role for CTLA-4 in the regulation of T cell responses. We also describe preclinical and clinical results that indicate manipulation of CTLA-4 has considerable promise as a strategy for the immunotherapy of cancer.

Integrity signals

Registry

Crossref · 10.1038/ni0702-611

Cites

93 of 93 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
Self-citation
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4
Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.
Dranoff, G., Jaffee, E. M., Lazenby, A., Golumbek, P. T., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D. M., & Mulligan, R. C. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3539 · Cited by 2,822
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245
Self-citation
Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4
Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W., & Sakaguchi, S. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.303 · Cited by 2,233
CTLA-4 can function as a negative regulator of T cell activation
Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., Thompson, C. B., & Bluestone, J. A. (1994) · Immunity · doi:10.1016/1074-7613(94)90071-x · Cited by 2,222
Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation
Read, S., Malmström, V., & Powrie, F. M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.295 · Cited by 2,206
B7/CD28 Costimulation Is Essential for the Homeostasis of the CD4+CD25+ Immunoregulatory T Cells that Control Autoimmune Diabetes
Salomon, B. L., Lenschow, D. J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A. H., & Bluestone, J. A. (2000) · Immunity · doi:10.1016/s1074-7613(00)80195-8 · Cited by 2,058
The B7–CD28 superfamily
Sharpe, A. H., & Freeman, G. J. (2002) · Nature reviews. Immunology · doi:10.1038/nri727 · Cited by 1,759
CTLA-4 is a second receptor for the B cell activation antigen B7.
Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of experimental medicine · doi:10.1084/jem.174.3.561 · Cited by 1,685 · cited 1×
“The finding that soluble recombinant CTLA-4 binds the same ligands as CD28, but with considerably higher avidity, offered the tantalizing suggestion that the two molecules have related function”
Background
Clonal Expansion Versus Functional Clonal Inactivation: A Costimulatory Signaling Pathway Determines The Outcome Of T Cell Antigen Receptor Occupancy
Mueller, D. L., Jenkins, M. K., & Schwartz, R. H. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.002305 · Cited by 1,505
The Central Role of CD4+ T Cells in the Antitumor Immune Response
Hung, K., Hayashi, R., Lafond-Walker, A., Lowenstein, C., Pardoll, D., & Levitsky, H. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.12.2357 · Cited by 1,345
A new member of the immunoglobulin superfamily—CTLA-4
Brunet, J., Denizot, F., Luciani, M., Roux-Rouquié, M., Suzan, M., Mattéi, M., & Golstein, P. (1987) · Nature · doi:10.1038/328267a0 · Cited by 1,307
Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor Antigens
Huang, A. Y.-C., Golumbek, P. T., Ahmadzadeh, M., Jaffee, E. M., Pardoll, D. M., & Levitsky, H. I. (1994) · Science · doi:10.1126/science.7513904 · Cited by 1,159
Tumor Rejection After Direct Costimulation of CD8 + T Cells by B7-Transfected Melanoma Cells
Townsend, S. E., & Allison, J. P. (1993) · Science · doi:10.1126/science.7678351 · Cited by 1,139
Self-citation
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4
Chen, L., Ashe, S., Brady, W. A., Hellström, I., Hellström, K. E., Ledbetter, J. A., McGowan, P., & Linsley, P. S. (1992) · Cell · doi:10.1016/s0092-8674(05)80059-5 · Cited by 1,050
Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation
van Elsas, A., Hurwitz, A. A., & Allison, J. P. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.3.355 · Cited by 1,020
Self-citation
Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25+ regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses
Sutmuller, R. P. M., van Duivenvoorde, L. M., van Elsas, A., Schumacher, T. N. M., Wildenberg, M. E., Allison, J. P., Toes, R. E. M., Offringa, R., & Melief, C. J. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.6.823 · Cited by 1,008
Self-citation
Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors
Linsley, P. S., Greene, J. L., Brady, W., Bajorath, J., Ledbetter, J. A., & Peach, R. (1994) · Immunity · doi:10.1016/s1074-7613(94)80021-9 · Cited by 1,006
Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation
Salomon, B. L., & Bluestone, J. A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.225 · Cited by 1,001
CTLA-4-Mediated Inhibition in Regulation of T Cell Responses: Mechanisms and Manipulation in Tumor Immunotherapy
Chambers, C. A., Kuhns, M. S., Egen, J. G., & Allison, J. P. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.565 · Cited by 1,000
Self-citation
T-cell regulation by CD28 and CTLA-4
Alegre, M., Frauwirth, K. A., & Thompson, C. B. (2001) · Nature reviews. Immunology · doi:10.1038/35105024 · Cited by 934
CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.
Krummel, M. F., & Allison, J. P. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2533 · Cited by 923
Self-citation
The Duration of Antigenic Stimulation Determines the Fate of Naive and Effector T Cells
Iezzi, G., Karjalainen, K., & Lanzavecchia, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80461-6 · Cited by 897
CTLA-4 ligation blocks CD28-dependent T cell activation.
Walunas, T. L., Bakker, C. Y., & Bluestone, J. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2541 · Cited by 801
Massive Expansion of Antigen-Specific CD8+ T Cells during an Acute Virus Infection
Butz, E. A., & Bevan, M. J. (1998) · Immunity · doi:10.1016/s1074-7613(00)80469-0 · Cited by 763
Induction of Peripheral T Cell Tolerance In Vivo Requires CTLA-4 Engagement
Perez, V. L., Parijs, L. V., Biuckians, A., Zheng, X. X., Strom, T. B., & Abbas, A. K. (1997) · Immunity · doi:10.1016/s1074-7613(00)80284-8 · Cited by 715
Secretory lysosomes
Blott, E. J., & Griffiths, G. M. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm732 · Cited by 703
T Cell Receptor Signaling Precedes Immunological Synapse Formation
Lee, K., Holdorf, A. D., Dustin, M. L., Chan, A. C., Allen, P. M., & Shaw, A. S. (2002) · Science · doi:10.1126/science.1067710 · Cited by 684
Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement
Linsley, P. S., Bradshaw, J., Greene, J. L., Peach, R., Bennett, K. L., & Mittler, R. S. (1996) · Immunity · doi:10.1016/s1074-7613(00)80480-x · Cited by 608
Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes.
Linsley, P. S., Greene, J. L., Tan, P., Bradshaw, J., Ledbetter, J. A., Anasetti, C., & Damle, N. K. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.6.1595 · Cited by 581
CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics
van der Merwe, P. A., Bodian, D. L., Daenke, S., Linsley, P., & Davis, S. J. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.3.393 · Cited by 551 · cited 1×
“The finding that soluble recombinant CTLA-4 binds the same ligands as CD28, but with considerably higher avidity, offered the tantalizing suggestion that the two molecules have related function”
Background
Cytotoxic T Lymphocyte Antigen-4 Accumulation in the Immunological Synapse Is Regulated by TCR Signal Strength
Egen, J. G., & Allison, J. P. (2002) · Immunity · doi:10.1016/s1074-7613(01)00259-x · Cited by 534
Self-citation
A Kinetic Basis For T Cell Receptor Repertoire Selection during an Immune Response
Savage, P. A., Boniface, J. J., & Davis, M. M. (1999) · Immunity · doi:10.1016/s1074-7613(00)80048-5 · Cited by 498
CTLA-4 regulates induction of anergy in vivo
Greenwald, R. J., Boussiotis, V. A., Lorsbach, R. B., Abbas, A. K., & Sharpe, A. H. (2001) · Immunity · doi:10.1016/s1074-7613(01)00097-8 · Cited by 428
Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.
Hurwitz, A. A., Foster, B. A., Kwon, E. D., Truong, T. N., Choi, E. M., Greenberg, N. M., Burg, M. B., & Allison, J. P. (2000) · PubMed · Cited by 425
Self-citation
CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation
Brunner-Weinzierl, M. C., Chambers, C. A., Chan, F. K.-M., Hanke, J., Winoto, A., & Allison, J. P. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.10.5813 · Cited by 419
Self-citation
T Cell Affinity Maturation by Selective Expansion during Infection
Busch, D. H., & Pamer, E. G. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.4.701 · Cited by 407
T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells
Kedl, R. M., Rees, W. A., Hildeman, D. A., Schaefer, B. C., Mitchell, T., Kappler, J. W., & Marrack, P. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.8.1105 · Cited by 407
Lymphoproliferation in CTLA-4–Deficient Mice Is Mediated by Costimulation-Dependent Activation of CD4 + T Cells
Chambers, C. A., Sullivan, T. J., & Allison, J. P. (1997) · Immunity · doi:10.1016/s1074-7613(00)80406-9 · Cited by 406
Self-citation
Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer
Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C. A., Feldhaus, A. L., Greenberg, N. M., Burg, M. B., & Allison, J. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8099 · Cited by 396
Self-citation
Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T Cells
Bensinger, S. J., Bandeira, A., Jordan, M. S., Caton, A. J., & Laufer, T. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.4.427 · Cited by 391
T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer
Mercader, M., Bodner, B. K., Moser, M. T., Kwon, P. S., Park, E. S. Y., Manecke, R. G., Ellis, T. M., Wojcik, E. M., Yang, D., Flanigan, R. C., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251140998 · Cited by 389
CTLA-4 blockade synergizes with tumor-derived granulocyte– macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma
Hurwitz, A. A., Yu, T. F.-Y., Leach, D. R., & Allison, J. P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10067 · Cited by 385
Self-citation
CTLA-4: a negative regulator of autoimmune disease.
Karandikar, N. J., Vanderlugt, C. L., Walunas, T. L., Miller, S. D., & Bluestone, J. A. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.2.783 · Cited by 376
Tyrosine Phosphorylation Controls Internalization of CTLA-4 by Regulating Its Interaction with Clathrin-Associated Adaptor Complex AP-2
Shiratori, T., Miyatake, S., Ohno, H., Nakaseko, C., Isono, K., Bonifacino, J. S., & Saito, T. (1997) · Immunity · doi:10.1016/s1074-7613(00)80346-5 · Cited by 345
Vitiligo in Patients with Melanoma
Rosenberg, S. A., & White, D. E. (1996) · Journal of Immunotherapy · doi:10.1097/00002371-199601000-00009 · Cited by 331
Characterization of CTLA-4 structure and expression on human T cells.
Lindsten, T., Lee, K. P., Harris, E. S., Petryniak, B., Craighead, N., Reynolds, P. J., Lombard, D. B., Freeman, G. J., Nadler, L. M., Gray, G. S., et al. (1993) · The Journal of Immunology · doi:10.4049/jimmunol.151.7.3489 · Cited by 316
Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4
Kearney, E. R., Walunas, T. L., Karr, R. W., Morton, P. A., Loh, D. Y., Bluestone, J. A., & Jenkins, M. K. (1995) · The Journal of Immunology · doi:10.4049/jimmunol.155.3.1032 · Cited by 312
Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine
van Elsas, A., Sutmuller, R. P. M., Hurwitz, A. A., Ziskin, J. L., Villaseñor, J., Medema, J. P., Overwijk, W. W., Restifo, N. P., Melief, C. J. M., Offringa, R., et al. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.4.481 · Cited by 308
Self-citation
T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.
Prasad, K. V., Cai, Y., Raab, M., Duckworth, B. C., Cantley, L. C., Shoelson, S. E., & Rudd, C. E. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.7.2834 · Cited by 295
Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Regulates the Unfolding of Autoimmune Diabetes
Lühder, F., Höglund, P., Allison, J. P., Benoist, C. O., & Mathis, D. J. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.187.3.427 · Cited by 290
Self-citation
CTLA-4 Blockade Reverses CD8+ T Cell Tolerance to Tumor by a CD4+ T Cell– and IL-2-Dependent Mechanism
Shrikant, P. A., Khoruts, A., & Mescher, M. F. (1999) · Immunity · doi:10.1016/s1074-7613(00)80123-5 · Cited by 288
Structural Analysis of CTLA-4 Function In Vivo
Masteller, E. L., Chuang, E., Mullen, A. C., Reiner, S. L., & Thompson, C. B. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5319 · Cited by 252 · cited 1×
“The finding that a cytoplasmic tail deletion mutant of CTLA-4, which is presumably deficient in signal transduction, can significantly delay, but not prevent, this lymphoproliferation suggests that competition with CD28 for B7 binding is not the only mechanism by which CTLA-4 functions and that CTLA-4 may also generat…”
Background
The specific direct interaction of helper T cells and antigen-presenting B cells.
Kupfer, A., Swain, S. L., Janeway, C. A., & Singer, S. J. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.16.6080 · Cited by 245
Cutting Edge: Lymphoproliferative Disease in the Absence of CTLA-4 Is Not T Cell Autonomous
Bachmann, M. F., Köhler, G., Ecabert, B., Mak, T. W., & Köpf, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1128 · Cited by 232
CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis
Perrin, P. J., Maldonado, J. H., Davis, T. A., June, C. H., & Racke, M. K. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.4.1333 · Cited by 226
Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression
Chuang, E., Alegre, M., Duckett, C. S., Noel, P. J., Heiden, M. G. V., & Thompson, C. B. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.1.144 · Cited by 225
The Role of CTLA‐4 in the Regulation and Initiation of T‐Cell Responses
Chambers, C. A., Krummel, M. F., Boitel, B., Hurwitz, A. A., Sullivan, T. J., Fournier, S., Cassell, D., Brunner-Weinzierl, M. C., & Allison, J. P. (1996) · Immunological Reviews · doi:10.1111/j.1600-065x.1996.tb00919.x · Cited by 210
Self-citation
Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages.
Yang, Y., Zou, J.-P., Mu, J., Wijesuriya, R., Ono, S., Walunas, T. L., Bluestone, J. A., Fujiwara, H., & Hamaoka, T. (1997) · PubMed · Cited by 197
The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells.
Kupfer, A., Swain, S. L., & Singer, S. J. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.165.6.1565 · Cited by 191
Cytotoxic T lymphocyte-associated molecule-4, a high avidity receptor for CD80 and CD86, contains an intracellular localization motif in its cytoplasmic tail
Leung, H. T., Bradshaw, J., Cleaveland, J. S., & Linsley, P. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.42.25107 · Cited by 191
B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28
Fallarino, F., Fields, P. E., & Gajewski, T. F. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.1.205 · Cited by 186
CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice
Tivol, E. A., Boyd, S. D., Mckeon, S., Borriello, F., Nickerson, P. W., Strom, T. B., & Sharpe, A. H. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.158.11.5091 · Cited by 185
Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein
Zhang, Y., & Allison, J. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.17.9273 · Cited by 181
Self-citation
Peptide Dose, Affinity, and Time of Differentiation Can Contribute to the Th1/Th2 Cytokine Balance
Rogers, P., & Croft, M. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.3.1205 · Cited by 179
Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol 3-kinase in Jurkat T cells.
Truitt, K. E., Hicks, C. M., & Imboden, J. B. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.3.1071 · Cited by 178
Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells
Iida, T., Ohno, H., Nakaseko, C., Sakuma, M., Takeda‐Ezaki, M., Arase, H., Kominami, E., Fujisawa, T., & Saito, T. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.9.5062 · Cited by 173
CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells.
Schneider, H. E., Prasad, K. V., Shoelson, S. E., & Rudd, C. E. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.181.1.351 · Cited by 164
In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance
Sotomayor, E. M., Borrello, I., Tubb, E. E., Allison, J. P., & Levitsky, H. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.20.11476 · Cited by 157
Self-citation
B7-1 or B7-2 Is Required to Produce the Lymphoproliferative Phenotype in Mice Lacking Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4)
Mandelbrot, D. A., McAdam, A. J., & Sharpe, A. H. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.2.435 · Cited by 142
Cytolytic T lymphocyte-associated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2.
Schneider, H., Martı́n, M., Agarraberes, F. A., Yin, L., Rapoport, I., Kirchhausen, T. L., & Rudd, C. E. (1999) · PubMed · Cited by 134
Blockade of CTLA-4 Enhances Host Resistance to the Intracellular Pathogen, Leishmania donovani
Murphy, M. L., Cotterell, S. E. J., Gorak, P. M. A., Engwerda, C. R., & Kaye, P. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.8.4153 · Cited by 133
Structural mechanisms of costimulation
Schwartz, J.-C. D., Zhang, X., Nathenson, S. G., & Almo, S. C. (2002) · Nature Immunology · doi:10.1038/ni0502-427 · Cited by 132
Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice.
MOKYR, M. B., Kalinichenko, T. V., Gorelik, L., & Bluestone, J. A. (1998) · PubMed · Cited by 130
Selective Activation and Expansion of High-Affinity CD4+ T Cells in Resistant Mice upon Infection with Leishmania major
Malherbe, L. P., Filippi, C. M., Julia, V., Foucras, G., Moro, M., Appel, H., Wucherpfennig, K. W., Guéry, J., & Glaichenhaus, N. (2000) · Immunity · doi:10.1016/s1074-7613(00)00075-3 · Cited by 130
Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo
Krummel, M. F., Sullivan, T. J., & Allison, J. P. (1996) · International Immunology · doi:10.1093/intimm/8.4.519 · Cited by 129
Self-citation
Interaction of the Cytoplasmic Tail of CTLA-4 (CD152) with a Clathrin-Associated Protein Is Negatively Regulated by Tyrosine Phosphorylation
Bradshaw, J. D., Lu, P., Leytze, G., Rodgers, J., Schieven, G. L., Bennett, K. L., Linsley, P. S., & Kurtz, S. E. (1997) · Biochemistry · doi:10.1021/bi971762i · Cited by 127
Cytolytic T Lymphocyte-Associated Antigen-4 and the TCRζ/CD3 Complex, But Not CD28, Interact with Clathrin Adaptor Complexes AP-1 and AP-2
Schneider, H., Martı́n, M., Agarraberes, F. A., Yin, L., Rapoport, I., Kirchhausen, T. L., & Rudd, C. E. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.4.1868 · Cited by 126
CTLA-4 regulates cell cycle progression during a primary immune response
Greenwald, R. J., Oosterwegel, M. A., van der Woude, D., Kubal, A., Mandelbrot, D. A., Boussiotis, V. A., & Sharpe, A. H. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200202)32:2 · Cited by 120
Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4 + T cell responses
Chambers, C. A., Kuhns, M. S., & Allison, J. P. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.15.8603 · Cited by 116
Self-citation
Protective Immunity to Nematode Infection Is Induced by CTLA-4 Blockade
McCoy, K. D., Camberis, M., & Gros, G. S. L. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.2.183 · Cited by 106
Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis
Hurwitz, A. A., Sullivan, T. J., Krummel, M. F., Sobel, R. A., & Allison, J. P. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(96)00168-3 · Cited by 102
Self-citation
Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells
Doyle, A. M., Mullen, A. C., Villarino, A. V., Hutchins, A. S., High, F. A., Lee, H. W., Thompson, C. B., & Reiner, S. L. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.7.893 · Cited by 102
The Composition of a Primary T Cell Response Is Largely Determined by the Timing of Recruitment of Individual T Cell Clones
Bousso, P., Levraud, J., Kourilsky, P., & Abastado, J. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.10.1591 · Cited by 82
Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice
Hurwitz, A. A., Sullivan, T. J., Sobel, R. A., & Allison, J. P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042684699 · Cited by 79
Self-citation
Antagonistic Roles for CTLA-4 and the Mammalian Target of Rapamycin in the Regulation of Clonal Anergy: Enhanced Cell Cycle Progression Promotes Recall Antigen Responsiveness
Vanasek, T. L., Khoruts, A., Zell, T., & Mueller, D. L. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5636 · Cited by 79
Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of CD4 + T cells
Kuhns, M. S., Epshteyn, V. A., Sobel, R. A., & Allison, J. P. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220423597 · Cited by 66
Self-citation
Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase proteinin vivo
Gabay, C., Gigley, J. P., Sipe, J. D., Arend, W. P., & Fantuzzi, G. (2001) · European Journal of Immunology · doi:10.1002/1521-4141(200102)31:2 · Cited by 61
Absence of CTLA-4 Lowers the Activation Threshold of Primed CD8+ TCR-Transgenic T Cells: Lack of Correlation with Src Homology Domain 2-Containing Protein Tyrosine Phosphatase
Gajewski, T. F., Fallarino, F., Fields, P. E., Rivas, F. V., & Alegre, M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.3900 · Cited by 49
Cytotoxic cells : basic mechanisms and medical applications
Sitkovsky, M. V., & Henkart, P. A. (2000) · Medical Entomology and Zoology · Cited by 34
Augmentation of CTLA-4 expression by wortmannin: involvement of lysosomal sorting properties of CTLA-4
Oki, S., Kohsaka, T., & Azuma, M. (1999) · International Immunology · doi:10.1093/intimm/11.9.1563 · Cited by 17

Sorted by citations

Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2005) · Nature · doi:10.1038/nature04444 · Cited by 4,057
Self-citation
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Self-citation
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
“Proposed mechanisms for such inhibitory signals include direct inhibition at the TCR immune synapse, inhibition of CD28 or its signaling pathway, or increased mobility of T cells leading to decreased ability to interact with APCs.(9,12,13) CTLA-4 itself is subject to regulation, particularly by localization within the…”
Background
The B7 family revisited
Greenwald, R. J., Freeman, G. J., & Sharpe, A. H. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115611 · Cited by 2,318
Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease
Ueda, H., Howson, J. M. M., Esposito, L., Heward, J., Snook, Chamberlain, G., Rainbow, D. B., Hunter, K. M. D., Smith, A. N., Di Genova, G., et al. (2003) · Nature · doi:10.1038/nature01621 · Cited by 2,175

See all 940

Authors: Egen, J. G., Kuhns, M. S., & Allison, J. P.
Affiliations: Howard Hughes Medical Institute (US)
Corresponding author: Allison, James P.
ORCID: Egen, Jackson G.
Kuhns, Michael S.
Allison, James P.
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2002-07
Volume: 3
Issue: 7
Pages: 611-618
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni0702-611
OpenAlex: W2140460887
Cited by: 940
References: 93
Citations by year: 2026: 10 · 2025: 15 · 2024: 30 · 2023: 34 · 2022: 45 · 2021: 50 · 2020: 43 · 2019: 33 · 2018: 27 · 2017: 36 · 2016: 28 · 2015: 32 · 2014: 31 · 2013: 38 · 2012: 25
FWCI: 5.88
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Howard Hughes Medical Institute
National Institutes of Health
National Cancer Institute (CA40041, R01CA057986, CA57986)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: CTLA-4, costimulatory receptors, CD28, T cell activation, T cell receptor signaling, T cell regulation, cancer immunotherapy, CTLA-4 blockade, immune checkpoint blockade
MeSH terms: Abatacept, Animals, Antigens, Differentiation, Cell Division, Colonic Neoplasms, Disease Models, Animal, Fibrosarcoma, Gene Expression Regulation, Humans, Immunotherapy, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Antigens, CD, Immunoconjugates, Mice, CTLA-4 Antigen

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

CTLA-4: new insights into its biological function and use in tumor immunotherapy

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks