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Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells
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Significance Immunosuppressive Tregs constitutively express CTLA-4, an immune checkpoint receptor. Addressing the role of CTLA-4 in Treg-suppressive function, we show that Treg-expressed CTLA-4, even in the absence of its cytoplasmic portion, promoted the conjugation of Tregs and antigen-presenting cells (APCs), leading to CTLA-4–dependent trogocytosis of CD80/CD86 and concomitant transfer of membrane fragments from APCs to the Treg cell surface. The depletion or blockade of CD80 by trogocytosis or solubilized CTLA-4, respectively, increased free PD-L1 by disrupting cis-CD80/PD-L1 heterodimers on APCs. Thus, Tregs can exert dual suppressive effects through the limitation of CD80/CD86 and up-regulation of free PD-L1 on APCs. Cancer immunotherapy with anti–CTLA-4 and anti–PD-1/PD-L1 blocking antibodies may enhance tumor immunity by hindering this Treg-mediated immune suppression.
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“T cells expressing CTLA4 on the surface can decrease CD80 and CD86 expressions on APCs by undergoing trans‐endocytosis and inhibiting CD28 signaling [297].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [297]
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Cites
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
CTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
Self-citationTakahashi, 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
Self-citationRead, S., Malmström, V., & Powrie, F. M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.295 · Cited by 2,206
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
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4
Qureshi, O. S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E. M., Baker, J., Jeffery, L. E., Kaur, S., Briggs, Z., et al. (2011) · Science · doi:10.1126/science.1202947 · Cited by 1,860
Mechanisms of Foxp3+ T Regulatory Cell-Mediated Suppression
Shevach, E. M. (2009) · Immunity · doi:10.1016/j.immuni.2009.04.010 · Cited by 1,787
Butte, M. J., Keir, M. E., Phamduy, T. B., Sharpe, A. H., & Freeman, G. J. (2007) · Immunity · doi:10.1016/j.immuni.2007.05.016 · Cited by 1,785
Takahashi, T., Kuniyasu, Y., Toda, M., Sakaguchi, N., Itoh, M., Iwata, M., Shimizu, J., & Sakaguchi, S. (1998) · International Immunology · doi:10.1093/intimm/10.12.1969 · Cited by 1,566
Self-citationRegulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,163
Self-citation
Cited by
Sorted by citations
Items 401–491 of 491
Arai, M., Kawakami, R., Nakamura, Y., Naito, Y., Motooka, D., Sugimoto, A., Kimoto, T., Ohkura, N., Mikami, N., & Sakaguchi, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.02.646742
“In addition to the role of CD80/CD86 for Treg induction by APCs, it has been shown that PD-L1 + DCs are potent in inducing antigen-specific Treg cells and that PD-L1 blockade inhibits the induction (Wang et al., 2008; Francisco et al., 2009).”
InfluentialSelf-citationDu, X., Wei, N., Wang, A., & Sun, G. (2025) · BMC Medical Genomics · doi:10.1186/s12920-025-02142-3
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Xiao, J., Guo, X., Gong, L., Li, Q., Dong, K., Guo, X., Li, H., Wang, T., Wu, W., Gan, C., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5220654
Singh, N., & Nigam, M. (2025) · Interdisciplinary biotechnological advances · doi:10.1007/978-981-96-4959-4_5
Mikami, N., Kawakami, R., Sugimoto, A., Arai, M., & Sakaguchi, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.13.659621
“They highly expressed Foxp3, CD25, and especially CTLA-4, which is essential for Treg suppressive function to reduce CD80/CD86 and increase free PD-L1 on antigen-presenting cells (APCs) (6, 32, 33) ( Fig.”
Self-citationColson, T. R., Cameron, J. J., Muendlein, H. I., Nolan, M.-A., Leiriao, J. L., Kim, J. H., Poltorak, A. N., & Li, X. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.24.665398
Zhao, Z., Zhang, J., Zhang, J., Liu, F., Wang, B., Zhou, Y., Li, X., Li, R., Ma, J., Wu, H., et al. (2025) · Oncology Letters · doi:10.3892/ol.2025.15211
“Tregs downregulate CD80/CD86 expression on antigen‑presenting cells via cytotoxic T‑lymphocyte associated protein 4 (CTLA‑4)‑dependent trogocytosis, weakening their co‑stimulatory function whilst releasing free programmed death‑ligand 1 (PD‑L1) to further suppress effector T cells (53).”
Modulation of T Cell Regulation by Interleukin-2 Agonists: Mechanisms and Clinical Implications
Sonak, S. S., Ishwarkar, S., Nimbarte, C., & Nimbarte, V. D. (2025) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.2025059823
Rigo, V., Amaro, A. A., Reggiani, F., Fenoglio, D., Martini, S., Altosole, T., Petito, M., Profumo, C., & Croce, M. (2025) · MedComm · doi:10.1002/mco2.70336
Wing, J. B., & Sakaguchi, S. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-824465-4.00276-3
Self-citationNishisaka, K., Sendo, S., Peral-Fanjul, A. D., Yamashita, M., Ichikawa, S., Okano, T., Yamada, H., Nishimura, K., Ueda, Y., & Saegusa, J. (2025) · Research Square · doi:10.21203/rs.3.rs-7246989/v1
Cellular Mechanism and Key Insights in Allergen Immunotherapy for Allergic Rhinitis
Wang, Z., Li, T., Wang, T., & Liu, H. (2025) · World Journal of Otorhinolaryngology - Head and Neck Surgery · doi:10.1002/wjo2.70050
“IL ‐ 10 can increase the concentration of IgG4, TGF ‐ β can upregulate the level of IgA, and IL ‐ 35 can decrease the production and secretion of IgE [31].”
Jing, Y., Li, Z., Bai, F., Yan, Y., Yan, L., Liu, W., Wang, Q., Zhao, L., Zhu, Y., Sun, G., et al. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00743
“In 2021, Murat Tekguc and his research team found that Treg cells can suppress immune responses through Cytotoxic T-lymphocyte-associated Antigen-4 (CTLA-4) by downregulating CD80/CD86 expression on antigen-presenting cells (APCs) and blocking the CD80/CD86-CD28 co-stimulatory interaction [37,38].”
Oudah, N. A., Saadi, K. A. A., & Ali, H. H. M. (2025) · Medical Journal of Babylon · doi:10.4103/mjbl.mjbl_458_23
Mechanisms of Resistance to Immunotherapies in Cancer
Lengyel, C. G. (2025) · Springer eBooks · doi:10.1007/978-3-032-00775-9_335
Effect of adipocytes on the function and activity of T cells in tumor microenvironment
Zhu, L., Xu, S., Ye, Y., Xiong, Y., & Li, Q. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1688342
“Tregs suppress immunity via CTLA-4/CD80/CD86 binding, IL-2 consumption, inhibitory cytokines, and direct cytotoxicity (21).”
Intestinal reengineering: Scientific advances in intestinal transplantation
Rong, Y., Nie, C.-Y., Zhou, J.-D., Wang, Z., Wu, D. W., Wu, S.-W., & Xie, Z. (2025) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v17.i10.111672 · Cited by 1
“Elevated circulating Treg levels correlate with FoxP3 expression and suppression of DC co-stimulation via CTLA-4-mediated downregulation of CD80/CD86, thereby attenuating effector T cell proliferation[104,105].”
Na, H. K., Hong, T. H., Lee, C., Yang, Y. H., Kim, H. E., Park, B. J., Kim, H. K., & Kim, D. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.27.690370
“The dominance of T REG and CTLA4-reliant suppression in primary tumors suggests that CTLA4-based strategies or dendritic cell activation could synergize with PD-1 blockade in the mucosal niche [20].”
UTP3: A Prognostic Marker in Hepatocellular Carcinoma and Its Role in Immunity and Epigenetics
Xu, Y., Zhang, S., Wei, G., Lv, Y., Dai, L., Li, C., & Wang, M. (2025) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.70632
“CTLA ‐ 4 and TIGIT intensify this via sequential inhibition, including CTLA ‐ 4's competition for B7 ligands to thwart CD28 signaling [69].”
Erbe, A. K., Feils, A. S., Gao, A., VandenHeuvel, S. N., Boyenga, S., Hampton, A. A., Heck, M., Zaborek, J., Spiegelman, D., Tsarovsky, N. W., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.11.693807
“45, 79 In tumors, Treg cytotoxicity has primarily been associated with suppression of effector lymphocytes, 80 yet direct tumor cell killing by Tregs has remained largely anecdotal.”
Mei, S., Alchahin, A. M., Τσέα, Ι., Kfoury, Y. S., Hirz, T., Jeffries, N. E., Zhao, T., Xu, Y., Zhang, H., Sarkar, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25101129
Mei, S., Alchahin, A. M., Τσέα, Ι., Kfoury, Y. S., Hirz, T., Jeffries, N. E., Zhao, T., Xu, Y., Zhang, H., Sarkar, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25101139
Yang, L., Chen, X., Lee, C., Shi, J., Lawrence, E. B., Zhang, L., Li, Y., Gao, N., Jung, S. Y., Creighton, C. J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22767404
Yang, L., Chen, X., Lee, C., Shi, J., Lawrence, E. B., Zhang, L., Li, Y., Gao, N., Jung, S. Y., Creighton, C. J., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22767401
Shukshin, A. A., Rubinstein, A. A., Golovkin, A. S., Moiseeva, O. M., & Kudriavtsev, I. V. (2025) · Medical academic journal · doi:10.17816/maj641689
Ma, Y., Sun, M., Qu, C., Jin, S., Yang, Z., Liu, H., Wang, Z., Wu, X., Hao, C., & Jin, Y. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.173287
Lu, Y., Guo, H., Guo, T., Zhang, L., & Pan, X. (2026) · Discover Oncology · doi:10.1007/s12672-026-04710-0
“…are pivotal suppressors mediating tumor immune escape, primarily through the secretion of immunosuppressive cytokines such as IL-10 and TGF-β [18, 19], or via immune checkpoint molecules including CTLA-4 and PD-1, which directly inhibit the activation and proliferation of effector T cells [20, 21].”
Ma, J., Xu, F., Wang, M., Zhang, S., Sang, J., Chen, H., Wen, F., Ge, R., Xie, Q., Wei, Z., et al. (2026) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-026-04317-y
“CD80 and CD86 act as co-stimulatory signals, playing a critical role in antigen presentation [21].”
Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy
Li, W., & Tong, J. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1787421
“By increasing the expression of CTLA-4 and PD-1, Tregs significantly suppress the cytotoxicity of effector cells, thereby strengthening tumor-associated immune suppression (Aksoylar and Boussiotis, 2020; Tekguc et al., 2021; Ding et al., 2024).”
Activation and lineage specific Lag3 expression dynamics in T cells
Khaled, C., kim, S., Kim, D., & Min, B. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag039
“41,42 Since CTLA4 expression has been previously shown to undergo continuous cycling, with markedly higher levels in Treg cells, 16,40,43 we reasoned that Lag3 might follow a similar pattern.”
Toma, B., Tanasa, M. P., & Danciu, M. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189580
huang, K., Zhang, S., Liu, J., Yang, C., Zeng, G., & Li, B. (2026) · Physiological Genomics · doi:10.1152/physiolgenomics.00300.2025 · Cited by 1
Bonnin, E. (2022) · theses.fr (ABES) · doi:10.70675/fd80c953z7ef5z4ff7z8413z3bd284faeed4
Li, Y., Wang, L., Zhang, B., & Xu, F. (2026) · Acta Mechanica Sinica · doi:10.1007/s10409-025-25992-x
The biliary tree: A new frontier in mucosal immunology?
Guo, Y., Chouik, Y., Hao, Y., Kohlhepp, M. S., & Guillot, A. (2026) · Mucosal Immunology · doi:10.1016/j.mucimm.2026.04.006
Ekström-Rydén, V., Carneiro, A., Yachnin, J., Rohrberg, K. S., Smith, K. E., Ellmark, P., Eefsen, R. L., & Ullenhag, G. J. (2026) · ESMO Open · doi:10.1016/j.esmoop.2026.106068
“10 Ipilimumab, which inhibits the CTLA-4 receptor, was the first approved CPI for the treatment of cancer.”
Mulugeta, N., Peters, M. Q., Tobey, C., Wong, J., Spray, A. L. P., Armistead, B., Jiang, Y., Katz, R., Shree, R. S., Vojtech, L. N., et al. (2026) · American Journal of Reproductive Immunology · doi:10.1111/aji.70238
“A memory phenotype and elevated expression of these markers alters Treg functional capacity through interactions with antigen-presenting cells and increased capacity for IL-10 secretion [ 36, 37 ].”
Gonçalves-Pereira, M. H., Queiroz, C. P., Figueiredo, M. M., de Carvalho, I. L. Q., Ramos, M. F., Bento, G. A., Magalhães, T. V. B., Mafra, A. D. A., Diniz, L. M. O., da Costa, Ú. L., et al. (2026) · Journal of Medical Virology · doi:10.1002/jmv.70956
Mannion, J. M., Altenburger, L. M., Willit, H., Smith, N. P., Cashin, C. N., Clegg, J., Samanta, N., Barrera, V., Gammerdinger, W., Sui, S. H., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.04.722795
Ali, M., Akpinar, Z. F., Ovando-Ricardez, J. A., Casasent, T. D., Lam, T., Lin, J., Khanmammadova, N., Reville, P. K., Shih, D. J. H., Osunkoya, A. O., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.06.722652
Canning, A., Donohoe, E., Johnston, É., Lynch, K., Moosavizadeh, S., Wang, J., Leahy, M. J., Treacy, O., Ryan, A. E., & Ritter, T. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116837
Shao, Y., Yu, S., Zhang, M., Huang, Y., Dou, Z., Tian, B., & Lu, J. (2026) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiag067
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Jiang, Y., Xu, P., Gao, T., Wang, C., Fan, M., Tang, Z., Zheng, K., & Liu, P. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1725547
“This suppression of co-stimulatory signals, together with increased surface expression of PD-L1 (a molecule that inhibits T cell activation) on target cells, collectively inhibits T cell activation (18).”
Khamidova, F., Babaeva, Z., Jafarov, K., Kasimova, M., Yumashev, A., Dоniyоrоva, D., Norqobilova, R., Raxmatullayev, J., & Sardor, K. (2026) · Clinical & Translational Oncology · doi:10.1007/s12094-026-04451-0
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Li, H., Wu, R.-Y., Mao, X.-T., Zhou, X.-R., Hao, K., & Tian, H.-Y. (2026) · Chinese Journal of Polymer Science · doi:10.1007/s10118-026-3678-6
Waseem, S., Zhan, J., & Xiao, X. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125373
Mechanobiology of regulatory T cells: how cellular mechanics shape immune suppression
Muniz, V. A., Singh, V., Akkaya, B., & Kural, C. (2026) · npj Biological Physics and Mechanics. · doi:10.1038/s44341-026-00039-5 · Cited by 1
“Forcegenerationby theactincytoskeletonisrequired for synapse formation between a T cell and a target cell 13 , and co-receptors such as CTLA-4 can couple ligand binding to trans-endocytosis of CD80/ CD86 in activated T cells and Tregs 14 – 16 .”
Hepatocellular carcinoma tumor immune microenvironment: heterogeneity and therapeutic strategies
Mao, T., Jiang, J., Liu, P., Zhao, Y., Zhong, L., Zhang, Z., Wu, K., & Xia, L. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2026.04
Yang, J., Zhou, H., Ma, X., Zhou, X., Wei, S., ZHAO, Y., & Li, C. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1871133
Brain-specific regulatory T cell mediators
Bharadwaj, A., Ashwani, Bhamboo, N., Vikash, & Gugulothu, D. B. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-43846-2.00008-8
Xin, S., Qin, W., Su, J., Li, R., Li, G., Zhang, Z. D., Wang, C., Zhu, Y., Feng, L., & Gao, Z. (2026) · European journal of medical research · doi:10.1186/s40001-026-04821-y
“Related research shows Tregs could highly express CTLA-4, which could degrade CD80/CD86 molecules through ’endocytosis’ [54], thereby directly reducing the co-stimulatory capacity of antigen-presenting cells (APCs).”
Ou, C., Qi, L., Lai, H., Ye, J., Tian, X., & Li, Z. (2026) · Oral Oncology · doi:10.1016/j.oraloncology.2026.108017
Wang, T., Fei, H., Liu, X., Zhang, L., Liang, W., Wei, X., & Fei, F. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.154238
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Tiwari, R., Singh, S. S., Singh, V. K., Gautam, V., & Kumar, R. (2026) · Springer eBooks · doi:10.1007/978-981-95-9777-2_11
Wang, J., Zhou, J., Yang, B. Y., Wang, Y., & Liu, L. (2026) · Immunobiology · doi:10.1016/j.imbio.2026.153213
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Mikami, N. (2026) · Barrier Immunity · doi:10.1002/dni2.70013
Tang, B., Li, K., Chen, W., Xiao, J., Duan, Q., & Zhu, F. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1857616
Chandran, S., Tang, Q., Leung, J., Armstrong, B., Friedewald, J. J., Kirk, A. D., Laszik, Z. G., Goldstein, J., Morsheimer, M. M., & Vincenti, F. G. (2026) · American Journal of Transplantation · doi:10.1016/j.ajt.2026.07.016
Ma, J., Chen, J., Miao, T., Li, Y., Li, Y., Zhao, L., & Tian, H. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-08711-z
“Treg-expressed CTLA-4 can reduce CD80/CD86 availability on APCs through ligand capture and removal, thereby limiting the B7–CD28 co-stimulatory capacity available to tumor-reactive effector T cells [64, 89].”
Botchkova, E., Churov, A. V., & Arbatskiy, M. S. (2026) · Immuno · doi:10.3390/immuno6030049
Li, H., Shi, Y., An, W., Gao, Q., Hao, Y., Cui, Z., Zhang, F., Liu, Y., Chen, X., Wu, Q., et al. (2026) · Advanced Healthcare Materials · doi:10.1002/adhm.71511
Zhang, R., Zhang, A., Gao, T., Zhang, C., Liu, Y., & Liu, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1862165
Li, J., Pang, J., Wu, P., Wang, E., Zheng, S. J., 阮庆国, & Liu, R. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1881360
“Moreover, selective CTLA-4 ablation markedly impairs the suppressive function of Tregs both in vitro and in vivo , particularly by weakening their ability to downregulate CD80 and CD86 expression on dendritic cells (DCs) (36).”
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“174 Furthermore, in TMEs characterized by high MDSC infiltration, immunosuppression may persist despite PD-1 pathway blockade.”
Ma, S., Rong, J., Wu, X., Wu, X., Gao, Y., Li, H., & Yan, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1852152
“Clinical studies have demonstrated that in tumors with high PD-L1 expression, PD-1/PD-L1 inhibitors can abrogate the polarization of M2-type macrophages, reduce the secretion of IL-10, and promote the maturation of APCs (23).”
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Su, P., Zhang, Y., Yu, T., 王元宇, 牟一平, & Jin, W. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117338
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Sun, W., Zhang, Z., Wang, C., Huang, J., Cao, D., Peng, A., Jiang, H., & Zeng, W. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1933225
“Furthermore, Tregs represent a critical force in restraining APC hyperactivation; the reduced butyrate levels in the PI group may weaken Treg differentiation and induction, thereby compromising negative regulation of APCs (He et al., 2024; Tekguc et al., 2021).”
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“Mechanistically, Tregs can reduce the availability of CD80/CD86 costimulatory molecules on antigen-presenting cells (APCs) through a CTLA-4-dependent mechanism (120).”
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“A primary mode of action is the secretion of anti-in fl ammatory cytokines, including IL-10, TGF-b , and IL-35 (41, 114).”
InfluentialWen, Y., Cheng, N., Zhou, S., Zhu, H., & Ge, Q. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2026.1927654
“CTLA-4 is highly expressed on activated T cells and Tregs, inhibiting costimulatory signal transduction by competitively binding B7 molecules on APCs (Rudd et al., 2009; Topalian et al., 2016; Morad et al., 2021; Tekguc et al., 2021; Li G. et al., 2025).”
Darvishali, M. H., Rahimmanesh, I., Zaker, E., Nouri, N., Davoodi, A., Pour, F. S., Borzacchiello, A., Choi, Y. J., Gupta, V. K., Khanahmad, H., et al. (2026) · Chemical Engineering Journal · doi:10.1016/j.cej.2026.182065
T-cell exhaustion and senescence in cancer: Regulatory circuits and therapeutic state engineering
Han, J., Lyu, X., Wu, M., Lin, C., Zhou, Y., & Wang, W. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218841
Tertiary lymphoid structures for anti-tumor immunotherapy
Yu, L., Liu, H., Zha, X., Jiang, Z., Zhang, H., Wang, T., & Li, Z. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189723
Ye, Y., Zheng, H., Duan, J., Mo, L., Liao, Y., Zheng, Y., Li, L., Zheng, P., Han, H., Li, C., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.118074
Macrophage Trogocytosis of Tumor Cells Drives the Immunosuppression of Tumor Microenvironment
Liang, C., He, J., Zhuang, W., Lei, Y., Jiang, Y., Ma, X., Liu, P., Jiang, Z., Li, Y., & Xie, H.-Y. (2026) · Advanced Science · doi:10.1002/advs.77518
Immune‐Cell Dynamics in the Tumor Microenvironment: Implications for Cancer Therapy
Pin, G., Xie, Y., Song, R., Yang, M., Lin, Z., Guan, C., Wang, Z., Wen, J., & Chen, G. (2026) · MedComm · doi:10.1002/mco2.71040
“This reduces CD28 signaling in effector T cells [ 208 ].”
Pan-cancer biomarkers of immune therapy resistance: mechanisms and clinical translation
Wang, C., & Yang, D. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1895670
“…of antigen-presenting-cell costimulation, limit the availability of IL-2, and other dependent immunoregulatory mechanisms, tumor-infiltrating Tregs can restrict the activation, expansion, and cytotoxic function of CD8 + T cells (Geels et al., 2024; Tekguc et al., 2021; Noyes et al., 2022).”
Drow, T., Doglio, M., Grimm, A., DeVault-Nelson, V., Hoover, M., McKinney, B., Tripathi, S. K., Mellen, J., Milazewski, M., Zarin, P., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.05.756761
“Interestingly, consistent with direct B cell engagement, CAR19 EngTreg mediated CD19 trogocytosis of primary B cells; observations consistent with previous reports of robust trogocytosis of OX40L by OX40L-CAR nTreg ( 41, 60 ).”
In vivo membrane engineering: An approach to remodeling cell interfaces
Jin, J., Gao, J., & Jiang, X. (2026) · Acta Biomaterialia · doi:10.1016/j.actbio.2026.10.026
Nygård, L., Laine, A., Jartti, A., Schroderus, A., Pitkänen, V., Pfajfer, L., Knip, M., Veijola, R., Ilonen, J., Toppari, J., et al. (2026) · The Journal of Immunology · doi:10.1093/jimmun/vkag276
The trajectory of gout: mapping pathogenic cell states from flares to tophus
Li, S., Zhou, X., Liu, Z., Dalbeth, N., Xu, H., & Hua, Y. (2026) · Rheumatology · doi:10.1093/rheumatology/keag581
Non-cell-autonomous removal of protein aggregates via trogocytosisPreprint
Kimura, Y., Satoh, K., Chavan, A. R., Kasberg, W., Silva, M., Qiu, W., Iyer, N., Innerberger, M., Siwanowicz, I., Pope, S. D., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.13.758691
Stealth CAR-Tregs evade CD3 antibody therapy and skew immune responses toward regulationPreprint
Blein, T., Ayas, N., Charbonnier, S., Gil, A., Haddouche, A., Hassan, J., Rabaux, L., Andre, I., Waldmann, H., Lamarthée, B., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.13.758862
Next‐Generation CAR‐T Cell Therapy: From Modular Design to Clinical Expansion
Bai, Y.-S., Qin, J.-T., Dai, Z.-J., Yan, R., Yang, Y., & Wang, W.-G. (2026) · Exploration · doi:10.1002/exp2.70230
“This is particularly evident in solid tumours, where Treg infiltration may mediate immunosuppression through the CTLA-4 receptor, reducing the cytotoxic efficacy of CAR-T cells [ 87, 88 ].”
King, T., Gonzalez, E. R., Torres, E. T. R., & Finley, S. D. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.16.759478
Wu, L., Yao, H. Y., Fu, Z. J., Luo, R. H., & Zhou, S. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1909663
Glioblastoma as a dynamic tumor ecosystem: from molecular alterations to therapeutic translation
Górecki, L. (2026) · Experimental Hematology and Oncology · doi:10.1186/s40164-026-00854-5
“High CTLA-4 expression enables Tregs to competitively engage CD80/CD86 on antigen-presenting cells (APCs), thereby limiting co-stimulatory signaling and suppressing downstream pathways mediated by NF-κB, AP-1, and NF-AT [332].”
Metadata
- Authors
- Tekguc, M., Wing, J. B., Osaki, M., Long, J., & Sakaguchi, S.
- Affiliations
- Laboratory of Experimental Immunology, World Premier International (WPI) Immunology Frontier Research Center (IFReC), Osaka University, Suita 565-0871, Japan;
- Immunology Frontier Research Center, The University of Osaka (JP)
- Kyoto University (JP)
- Corresponding author
- Sakaguchi, Shimon
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2021-07-23
- Volume
- 118
- Issue
- 30
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8325248
- OpenAlex
- W3185714107
- Cited by
- 490
- References
- 53
- Citations by year
- 2026: 116 · 2025: 123 · 2024: 114 · 2023: 72 · 2022: 61 · 2021: 4
- FWCI
- 23.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OUKA (Osaka University Knowledge Archive) (Osaka University) (submittedVersion)
- Funders
- MEXT | Japan Society for the Promotion of Science (16H06295, 18K07175)
- MEXT | JST | Core Research for Evolutional Science and Technology (JP 19gm0010005)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- regulatory T cells, CTLA-4, trogocytosis, CD80, CD86, PD-L1, antigen-presenting cells, immune checkpoint, cancer immunotherapy
- MeSH terms
- Trogocytosis, Animals, Antigen-Presenting Cells, Dendritic Cells, Female, Lymphocyte Activation, Mice, Inbred BALB C, Mice, Inbred C57BL, B7-1 Antigen, Mice, Knockout, T-Lymphocytes, Regulatory, Mice, B7-2 Antigen, B7-H1 Antigen, CTLA-4 Antigen
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