The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation
Open accessPublished version of a preprint
Abstract
Immune checkpoint blockade, exemplified by antibodies targeting the PD-1 receptor, can induce durable tumor regressions in some patients. To enhance the efficacy of existing immunotherapies, we screened for small molecules capable of increasing the activity of T cells suppressed by PD-1. Here, we show that short-term exposure to small-molecule inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) significantly enhances T-cell activation, contributing to antitumor effects in vivo, due in part to the derepression of NFAT family proteins and their target genes, critical regulators of T-cell function. Although CDK4/6 inhibitors decrease T-cell proliferation, they increase tumor infiltration and activation of effector T cells. Moreover, CDK4/6 inhibition augments the response to PD-1 blockade in a novel ex vivo organotypic tumor spheroid culture system and in multiple in vivo murine syngeneic models, thereby providing a rationale for combining CDK4/6 inhibitors and immunotherapies. Significance: Our results define previously unrecognized immunomodulatory functions of CDK4/6 and suggest that combining CDK4/6 inhibitors with immune checkpoint blockade may increase treatment efficacy in patients. Furthermore, our study highlights the critical importance of identifying complementary strategies to improve the efficacy of immunotherapy for patients with cancer. Cancer Discov; 8(2); 216–33. ©2017 AACR. See related commentary by Balko and Sosman, p. 143. See related article by Jenkins et al., p. 196. This article is highlighted in the In This Issue feature, p. 127
Overview
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
Verification
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“cyclin-dependent kinase inhibitors 4 and 6 (CDK4/6) facilitate T cell activation, resulting in a higher number of tumour-infiltrating T cells in PDOs, cultivated over several days in a microfluidic 3D chip setup.”
From Human disease models in drug development (2023) · cites this paper as [129]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“CDK4/6 inhibition also showed high in vitro and in vivo activity and synergy with anti-PD-1 blocking antibodies129.”
From Human disease models in drug development (2023) · cites this paper as [129]
In the citing paper
“activation of effector T (TEFF) cells upon nuclear factor of activated T cells 1 (NFATC1, best known as NFAT) signaling and interleukin-2 (IL2) secretion (Deng et al., 2018)”
From Immunomodulation by targeted anticancer agents (2021) · cites this paper as Deng et al., 2018
In the citing paper
“CDK4/6 inhibition is also able to stimulate PD-1 expressing T-cells in vitro and enhance T cell infiltration (Deng et al., 2017).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Deng et al., 2017
In the citing paper
“This enhancement is driven at least in part by CDK6-induced phosphorylation of NFAT4.”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Deng et al., 2017
In the citing paper
“Combining palbociclib with a PD-1 blockade enhanced tumor regression and improved overall survival in mouse xenograft models of colon adenocarcinoma (Deng et al., 2017; Zhang et al., 2018).”
From CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought (2018) · cites this paper as Deng et al., 2017
In the citing paper
“CDK4/6 inhibitors improved the efficacy of α-PD-1 in murine models by enhancing lymphocyte infiltration and TIL activities [245–248].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [248]
In the citing paper
“We also recently demonstrated that CDK6, but not CDK4, phosphorylates NFAT family transcription factors to promote T cell activation and enhance the anti-tumor immune response[7].”
From Development of dual and selective degraders of cyclin-dependent kinases 4 and 6 (2019) · cites this paper as [7]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
STAR: ultrafast universal RNA-seq aligner
Dobin, A., Davis, C. A., Schlesinger, F., Drenkow, J., Zaleski, C., Jha, S., Batut, P., Chaisson, M., & Gingeras, T. R. (2013) · Bioinformatics · doi:10.1093/bioinformatics/bts635 · Cited by 51,709
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838 · cited 12×
“The digested NFATc3 and His-GB1 were separated and further purified using size exclusion chromatography (GE Healthcare Life Sciences “Superdex 75 10/300 GL”).”
BackgroundInfluentialNear-optimal probabilistic RNA-seq quantification
Bray, N. L., Pimentel, H., Melsted, P., & Pachter, L. (2016) · Nature Biotechnology · doi:10.1038/nbt.3519 · Cited by 9,723 · cited 11×
“The digested NFATc3 and His-GB1 were separated and further purified using size exclusion chromatography (GE Healthcare Life Sciences “Superdex 75 10/300 GL”).”
BackgroundMethodInfluentialNivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · cited 11×
“The digested NFATc3 and His-GB1 were separated and further purified using size exclusion chromatography (GE Healthcare Life Sciences “Superdex 75 10/300 GL”).”
BackgroundInfluentialMutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · cited 11×
“The digested NFATc3 and His-GB1 were separated and further purified using size exclusion chromatography (GE Healthcare Life Sciences “Superdex 75 10/300 GL”).”
BackgroundInfluentialTumor-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 · cited 3×
“The discovery of immune checkpoint receptors, such as CTLA-4 and PD-1 (5-9), that repress the activity of anti-tumor T cells, led to the development of blocking antibodies directed against these co-inhibitory receptors or their ligands, including ipilimumab (anti-CTLA-4), pembrolizumab (anti-PD-1), nivolumab (anti-PD1…”
BackgroundNeoantigens in cancer immunotherapy
Schumacher, T. N., & Schreiber, R. D. (2015) · Science · doi:10.1126/science.aaa4971 · Cited by 4,783 · cited 11×
“As Kras mutant GEMMs are not responsive to checkpoint blockade (3,44), in part due to a low levels of somatic mutations (45), we utilized the murine syngeneic colon adenocarcinoma model MC38.”
BackgroundMethodInfluential
Cited by
Sorted by citations
Items 701–776 of 776
Huang, X., Jayabalan, D. S., Liberto, M. D., Chen, Z., Ely, S. A., Mark, T. M., Lin, G., Niesvizky, R., & Chen‐Kiang, S. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.14.681840
“…in various preclinical solid cancer models; it triggers anti-tumor immunity 62 , augments anti-tumor immunity by enhancing T-cell activation 63 , elicits a cancer cell program that enhances the checkpoint blockade therapy 64 ; and promotes tumor immunity through induction of T cell memory…”
Targeting cellular senescence for cancer therapy
Abduljabbar, R., Liu, Y., Mussa, A., Abdu, A. M. A., Man, Y., Chen, Q., & Liu, Z. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.126297
Introduction of triple negative breast cancer and precision medicine
Rane, B. R., Sawant, R. R., Mhatre, P. V., & Kothawade, S. N. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-33565-5.00004-9
Hu, S.-W., Yeh, M., He, Y., Wei, Y.-L., Cheng, F., Yeh, Y., Huynh, T. K., Liu, P.-T., Hu, D.-W., Chang, T.-H., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102429 · Cited by 1
“41 We found that DEHP treatment significantly upregulated CDK4 mRNA (Figure 6B) and protein levels (Figure 6C) in both MCF-7 and MDA-MB-231 breast cancer cells.”
Self-citationγδ T cells and resistance to CDK4/6 inhibitors in breast cancer
Kepp, O., & Kroemer, G. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08149-z
Tümör-Bağışıklık Hücre Etkileşimlerini Araştırmak İçin Biyomühendisliksel Yöntemler
Topal, T., & Uzun, Z. E. (2025) · Gazi Üniversitesi Fen Fakültesi Dergisi · doi:10.63716/guffd.1768168
Wan, Y., Wang, J., O’Connor, T. N., Kumarasamy, V. M., Sanidas, I., Abrams, S. I., Witkiewicz, A. K., & Knudsen, E. S. (2025) · npj Breast Cancer · doi:10.1038/s41523-025-00845-5
The Potential Role of Immunotherapy in ER-positive Breast Cancer
Fa’ak, F. (2025) · Current Breast Cancer Reports · doi:10.1007/s12609-025-00622-0
“In preclinical studies, CDK4/6i promotes tumor antigen presentation, suppresses Tregs proliferation, and increases TILs and cytotoxic T-cell-mediated clearance of tumor cells [47, 48].”
Zhang, Z., Wang, G., Zhong, K., Chen, Y., Yang, N., Lu, Q., Yuan, B., Wang, Z., Li, H., Guo, L., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561162
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766319
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561060
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766322
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766325
Liang, J., Sun, G., Pan, X., Zhang, M., Shen, P., Zhu, S., Zhao, J., Zheng, L., Zhao, J., Chen, Y., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22735557
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561033
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766331
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561042
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561039
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561048
Huang, Y., Chen, D., Bai, Y., Zhang, Y., Zheng, Z., Fu, Q., Yi, B., Jiang, Y., Zhang, Z., & Zhu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26705250
Self-citationHuang, Y., Chen, D., Bai, Y., Zhang, Y., Zheng, Z., Fu, Q., Yi, B., Jiang, Y., Zhang, Z., & Zhu, J. (2024) · Figshare · doi:10.6084/m9.figshare.25591495
Self-citationYang, 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
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561045
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766310
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561054
Huang, Y., Chen, D., Bai, Y., Zhang, Y., Zheng, Z., Fu, Q., Yi, B., Jiang, Y., Zhang, Z., & Zhu, J. (2024) · Figshare · doi:10.6084/m9.figshare.25591342
Self-citationKim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561051
Huang, Y., Chen, D., Bai, Y., Zhang, Y., Zheng, Z., Fu, Q., Yi, B., Jiang, Y., Zhang, Z., & Zhu, J. (2024) · Figshare · doi:10.6084/m9.figshare.26705247
Self-citationLiang, J., Sun, G., Pan, X., Zhang, M., Shen, P., Zhu, S., Zhao, J., Zheng, L., Zhao, J., Chen, Y., et al. (2023) · Figshare · doi:10.6084/m9.figshare.22735551
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766316
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766328
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561057
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561036
Kim, C. G., Kim, M. H., Kim, J. H., Kim, S.-G., Kim, G. M., Kim, T. Y., Ryu, W.-J., Kim, J. Y., Park, H. S., Park, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561063
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
Wu, Y., Shrestha, P., Heape, N. M., & Yarchoan, R. (2022) · Figshare · doi:10.6084/m9.figshare.19766313
Xu, Q., Li, C., Zhao, A., Xie, J., Lu, M., Huang, M., Huang, W., & Huang, R. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.153186
Self-citationCardiovascular toxicity of cyclin-dependent kinase 4 and 6 inhibitors
Zhang, J., Ma, Z., Chen, P., Tian, L., Fang, F., & Li, J. (2025) · Journal of Cardio-oncology · doi:10.1097/co9.0000000000000007
Immune Checkpoints in Peritoneal Carcinomatosis : HLA-G, PD-L1 & the Impact of Cancer Therapies
Ullah, M. (2019) · theses.fr (ABES) · doi:10.70675/6b7b16b5z18e9z4f6cz8371z93d206b34a18
Ciblage thérapeutique de la protéine CDK6 dans les leucémies aiguës myéloïdes
Brault, L. M. (2022) · theses.fr (ABES) · doi:10.70675/26bca708z5a9az4d80z85bfz9159b330b1e8
Lagarce, L., Gaiffe, A., Freppel, R., Storck, W., Cracowski, J., & Briet, M. B. (2026) · Therapies · doi:10.1016/j.therap.2026.03.005
Kurma, K., Bardol, T., Mollevi, C., Eslami‐S, Z., Garima, F., Alexandre, M., Bobrie, A., Lossaint, G., Massemin, B., D’Hondt, V., et al. (2026) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-026-03709-3 · Cited by 3
“Indeed, endocrine therapy and CDK4/6 inhibitors may partially restore immune activation in luminal disease [43].”
Wang, Y., Reshetnikova, E., Katuwal, N. B., Bharti, V., Pereira, M. S., Oppong, B. A., Lee, D. A., Mittra, A., Freud, A. G., & Vilgelm, A. E. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.04.19.719504
Role of small molecule-based drugs in cancer immunotherapy
Shah, U., Patel, M., Patel, A., Shah, P., Dwivedi, A. R., & Maheshwari, R. A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-41551-7.00014-x
Su, X., Kobayashi, T., Xiang, J., Xu, Y., Shajahan‐Haq, A. N., Mardani, M., Noordeen, S., O'Donnell, K. M., Kwakwa, K. A., Guan, D., et al. (2026) · Journal of bone oncology · doi:10.1016/j.jbo.2026.100765
“Although inhibiting the CDK4/6 pathway can modulate the immune system, by reducing regulatory T cells and myeloid derived suppressor cells (MDSCs) [13], and enhancing T cell activation [14 – 17].”
Hsieh, T., Kuo, H., Pan, C., Lin, Y.-C., Lin, B.-J., Chen, M. Y., & Chen, C.-H. (2026) · Biology Direct · doi:10.1186/s13062-026-00812-5
“In BC models, CDK4/6 inhibitors have also been shown to increase CD8 ⁺ T-cell infiltration and enhance responses to PD-1 blockade [44, 45].”
E, E. R. P., Seier, K., Gularte‐Mérida, R., Seffar, E., Dickson, M. A., Avutu, V., Banks, L. B., Chan, J. E., Chi, P., Gounder, M. M., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-014346
Takiguchi, C., Nakajima, S., Matsuida, H., Hanayama, H., Matsuishi, A., Saito, K., Hayashishita, S., Mitsui, D., Fujii, A., Yamaguchi, D., et al. (2026) · Journal of Gastroenterology · doi:10.1007/s00535-026-02443-z
Guo, X., Li, P., Hu, S., Ding, Y., Xie, B., Cai, Y., Chen, H., Li, X., Guo, S., Wang, Y., et al. (2026) · BMC Cancer · doi:10.1186/s12885-026-16176-y
“Beyond cell cycle blockade, CDK4/6 inhibitors enhance T-cell activity and antitumor immunity [34].”
Cui, J., Zhang, Y., Wu, Y., Zhang, G., Lan, J., & Wang, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1845921
“CDK4/ 6 inhibitors can also increase the in fi ltration of effector T cells into tumors, which may be related to the elevated levels of chemokines such as CXCL9 and CXCL10 following CDK4/6 inhibitors treat-ment (91).”
Self-citationCell Cycle Sensing Shapes Human T Cell Fate and Exhaustion ProgramsPreprint
Amouzgar, M., Murty, T., Favaro, P. M. B., Sotillo, E., Bruce, T., Ho, D., Lam, A. J., Tibshirani, R. J., Mackall, C. L., & Bendall, S. C. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.11.731737
Patient-derived organoid in vitro models for antibody-based immunotherapy in pediatric solid tumors
Koelewijn, J., Janda, C. Y., & van Noesel, M. M. (2026) · EJC Paediatric Oncology · doi:10.1016/j.ejcped.2026.100533
Gupta, R., Lakhanpal, S., Kumar, N., Nagraik, R., Ravi, K., Sharma, S., Abomughaid, M. M., Kumari, S., & Jha, N. K. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1844582
“Early-phase translational studies also suggest that CDK4/6 inhibitors may have a role in modulating tumor immune signaling and metabolism, potentially synergizing with immunotherapy (Gogolin et al., 2013; Deng et al., 2018).”
T cell activation and TCRs as an immunotherapeutic approach in cancer
Güney-Kalkan, S. (2026) · Letters in Drug Design & Discovery · doi:10.1016/j.lddd.2026.100450
Upadhyay, S., Khan, S., Bhardwaj, M., & Hassan, M. I. (2026) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2026.168364
Ávalos-Moreno, M., Vigato, A., Moresi, F., Japon-Ruiz, D., Beck, B., & Bisteau, X. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.17.738886
Владимирович, С. А., & Кононенко, И. Б. (2026) · Journal of Modern Oncology · doi:10.26442/18151434.2026.2.203708
Ku, Y., Zheng, Y., Ding, Y., Zhang, P., Wu, X., & Chen, Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167119
Zheng, C., Pan, Y., Zheng, D., & Pan, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1934879
Tang, Y., Zhu, Y., Liu, S., Han, X., Zhang, H., & Zhao, W. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1923129
“Immune checkpoint blockade (ICB) remains the most extensively investigated immunotherapeutic partner for CDK4/6 inhibitors because CDK4/6 inhibition can enhance antigen presentation and promote effector T-cell activity (4, 8).”
Self-citationThe molecular mechanics of CDK4/6 inhibitors: resistance pathways and combination strategies
Dharavath, A., Mishra, B. B., & Guru, S. K. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44611-5.00002-x
CDK4/6 inhibitors: Future perspectives
Morddune, S., Sutar, A. D., & Shukla, R. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44611-5.00009-2
The repurposing era of CDK4/6 in the treatment of various ailments
Joshi, R., Soni, D., Kaur, C. D., Ravi, N. K., Singh, P. K., & Gupta, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44611-5.00001-8
Çoban, E., Kurt, A. E., Akagündüz, F., Demirel, A., Tunç, M. A., Paçacı, B., Güren, A. K., Kocaaslan, E., Erel, P., Ağyol, Y., et al. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15176790
Coupling and uncoupling cell cycle and metabolism in CD8+ T cells
van Haften, F. J., Hepp, H. S., Biemond, M., & Arens, R. (2026) · Trends in Immunology · doi:10.1016/j.it.2026.09.001
Breast cancer immunogenicity as a spectrum: evolving concepts and therapeutic implications
Kay, J., Dixon-Douglas, J. R., Harris, M. A., van Geelen, C. T., & Loi, S. (2026) · Journal of Clinical Investigation · doi:10.1172/jci207634
“Although mechanisms remain unclear, upregulation of antigen presentation machinery, downregulation of regulatory T cells, influx of CD8 + T cells, and induction of immunological memory have all been observed following treatment with CDK4/6 inhibitors (89–91).”
Wu, J., Liu, X., & Wu, G. (2026) · Journal of Holistic Integrative Pharmacy · doi:10.1016/j.jhip.2026.09.001
Karthikeyan, M. C., Viswanathan, Y., Dinakaran, P., Manivannan, S., & Arockiam, A. J. V. (2026) · SN Comprehensive Clinical Medicine · doi:10.1007/s42399-026-02789-8
Klar, N. J., Goldberg, J. D., Tyagi, A., Leal, A., Hochman, T., Barbury, B., Darvishian, F., Kwa, M., Meyers, M., Novik, Y., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-11146137/v1
BindingDB Entry 50017151: Lessons Learned from Past Cyclin-Dependent Kinase Drug Discovery Efforts.
BindingDB (2023) · UC San Diego · doi:10.7270/q2bv7mpd
BindingDB Entry 50022804: Advances in SHP2 tunnel allosteric inhibitors and bifunctional molecules.
BindingDB (2026) · UC San Diego · doi:10.7270/q2v98dw4
BindingDB (2021) · UC San Diego · doi:10.7270/q23f4t3t
Lee, Y.-W., Li, W., & Lee, K.-D. (2026) · Journal of Cancer Research and Practice · doi:10.4103/ejcrp.ejcrp-d-26-00010
Metadata
- Authors
- Deng, J., Wang, E. S., Jenkins, R. W., Li, S., Dries, R., Yates, K., Chhabra, S., Huang, W., Liu, H., Aref, A. R., Ivanova, E., Paweletz, C. P., Bowden, M., Zhou, C. W., Herter-Sprie, G. S., Sorrentino, J. A., Bisi, J. E., Lizotte, P. H., Merlino, A. A., Quinn, M. M., Bufe, L. E., Yang, A., Zhang, Y., Zhang, H., Gao, P., Chen, T., Cavanaugh, M. E., Rode, A. J., Haines, E., Roberts, P. J., Strum, J. C., Richards, W. G., Lorch, J. H., Parangi, S., Gunda, V., Boland, G. M., Bueno, R., Palakurthi, S., Freeman, G. J., Ritz, J., Haining, W. N., Sharpless, N. E., Arthanari, H., Shapiro, G. I., Barbie, D. A., Gray, N. S., & Wong, K.-K.
- Affiliations
- NYU Langone Health (US)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
- 9G1 Therapeutics, Research Triangle Park, North Carolina.
- Brigham and Women's Hospital (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Barbie, David A.
- Gray, Nathanael S.
- Wong, Kwok-Kin
- ORCID
- Deng, Jiehui
- Wang, Eric S.
- Jenkins, Russell W.
- Li, Shuai
- Dries, Ruben
- Yates, Kathleen
- Chhabra, Sandeep
- Huang, Wei
- Liu, Hongye
- Aref, Amir R.
- Ivanova, Elena
- Paweletz, Cloud P.
- Bowden, Michaela
- Zhou, Chensheng W.
- Herter-Sprie, Grit S.
- Sorrentino, Jessica A.
- Bisi, John E.
- Lizotte, Patrick H.
- Yang, Annan
- Zhang, Hua
- Gao, Peng
- Chen, Ting
- Haines, Eric
- Roberts, Patrick J.
- Strum, Jay C.
- Richards, William G.
- Lorch, Jochen H.
- Parangi, Sareh
- Boland, Genevieve M.
- Bueno, Raphael
- Palakurthi, Sangeetha
- Freeman, Gordon J.
- Ritz, Jerome
- Haining, W. Nicholas
- Sharpless, Norman E.
- Arthanari, Haribabu
- Shapiro, Geoffrey I.
- Barbie, David A.
- Gray, Nathanael S.
- Wong, Kwok-Kin
- Venue
- Cancer Discovery
- Published
- 2018-02-01
- Volume
- 8
- Issue
- 2
- Pages
- 216-233
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC5809273
- OpenAlex
- W2766016994
- Cited by
- 770
- References
- 63
- Citations by year
- 2026: 62 · 2025: 111 · 2024: 83 · 2023: 109 · 2022: 115 · 2021: 104 · 2020: 96 · 2019: 61 · 2018: 29
- FWCI
- 22.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Damon Runyon Cancer Research Foundation (Damon Runyon) (DRG-2270-16)
- HHS | NIH | National Cancer Institute (NCI) (CA154303-05, CA179483-03, P01CA120964, 5R01CA163896-04, 5R01CA140594-07, 5R01CA122794-10, 5R01CA166480-04)
- Dana-Farber Cancer Institute (DFCI) (Medical Oncology Discovery Grant)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CDK4/6 inhibitors, antitumor immunity, T cell activation, anti-PD-1 therapy, immune checkpoint blockade, combination immunotherapy, tumor-infiltrating T cells, small-molecule immunomodulators
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Antineoplastic Agents, Humans, Lymphocyte Activation, Neoplasms, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, 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
