Zou, W., Wolchok, J. D. & Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 8, 328rv324 (2016).

Article 

Google Scholar
 

Sharma, P. et al. Immune checkpoint therapy-current perspectives and future directions. Cell 186, 1652–1669 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Iwasaki, A. & Medzhitov, R. Control of adaptive immunity by the innate immune system. Nat. Immunol. 16, 343–353 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Carroll, S. L., Pasare, C. & Barton, G. M. Control of adaptive immunity by pattern recognition receptors. Immunity 57, 632–648 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Demaria, O. et al. Harnessing innate immunity in cancer therapy. Nature 574, 45–56 (2019).

Article 
CAS 
PubMed 

Google Scholar
 

Cao, L. L. & Kagan, J. C. Targeting innate immune pathways for cancer immunotherapy. Immunity 56, 2206–2217 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lynch, C., Pitroda, S. P. & Weichselbaum, R. R. Radiotherapy, immunity, and immune checkpoint inhibitors. Lancet Oncol. 25, e352–e362 (2024).

Article 
CAS 
PubMed 

Google Scholar
 

Kornepati, A. V. R., Rogers, C. M., Sung, P. T. & Curiel, T. J. The complementarity of DDR, nucleic acids and anti-tumour immunity. Nature 619, 475–486 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Chiappinelli, K. B. et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 162, 974–986 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Roulois, D. et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 162, 961–973 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sheng, W. et al. LSD1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 174, 549–563 e519 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Maxwell, M. B. et al. ARID1A suppresses R-loop-mediated STING-type I interferon pathway activation of anti-tumor immunity. Cell 187, 3390–3408 e3319 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Zhang, Z. D. & Zhong, B. Regulation and function of the cGAS-MITA/STING axis in health and disease. Cell Insight 1, 100001 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Jiang, X. et al. Ubiquitin-induced oligomerization of the RNA sensors RIG-I and MDA5 activates antiviral innate immune response. Immunity 36, 959–973 (2012).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Goel, S. et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature 548, 471–475 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Deng, J. et al. CDK4/6 inhibition augments antitumor immunity by enhancing T-cell activation. Cancer Discov. 8, 216–233 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Fassl, A., Geng, Y. & Sicinski, P. CDK4 and CDK6 kinases: from basic science to cancer therapy. Science 375, eabc1495 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Alvarez-Fernandez, M. & Malumbres, M. Mechanisms of sensitivity and resistance to CDK4/6 Inhibition. Cancer Cell 37, 514–529 (2020).

Article 
CAS 
PubMed 

Google Scholar
 

Dietrich, C. et al. INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. Cancer Discov. 14, 446–467 (2024).

Article 
CAS 
PubMed 

Google Scholar
 

Arora, M. et al. Rapid adaptation to CDK2 inhibition exposes intrinsic cell-cycle plasticity. Cell 186, 2628–2643 e2621 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Cidado, J. et al. AZD4573 is a highly selective CDK9 inhibitor that suppresses MCL-1 and induces apoptosis in hematologic cancer cells. Clin. Cancer Res. 26, 922–934 (2020).

Article 
CAS 
PubMed 

Google Scholar
 

Parua, P. K. et al. A Cdk9-PP1 switch regulates the elongation-termination transition of RNA polymerase II. Nature 558, 460–464 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Hluchy, M. et al. CDK11 regulates pre-mRNA splicing by phosphorylation of SF3B1. Nature 609, 829–834 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Dubbury, S. J., Boutz, P. L. & Sharp, P. A. CDK12 regulates DNA repair genes by suppressing intronic polyadenylation. Nature 564, 141–145 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Iniguez, A. B. et al. EWS/FLI confers tumor cell synthetic lethality to CDK12 inhibition in Ewing sarcoma. Cancer Cell 33, 202–216 e206 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Quereda, V. et al. Therapeutic targeting of CDK12/CDK13 in triple-negative breast cancer. Cancer Cell 36, 545–558 e547 (2019).

Article 
CAS 
PubMed 

Google Scholar
 

Insco, M. L. et al. Oncogenic CDK13 mutations impede nuclear RNA surveillance. Science 380, eabn7625 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Guen, V. J. et al. CDK10/cyclin M is a protein kinase that controls ETS2 degradation and is deficient in STAR syndrome. Proc. Natl Acad. Sci. USA 110, 19525–19530 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Iorns, E. et al. Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Cancer Cell 13, 91–104 (2008).

Article 
CAS 
PubMed 

Google Scholar
 

You, Y. et al. Downregulated CDK10 expression in gastric cancer: association with tumor progression and poor prognosis. Mol. Med. Rep. 17, 6812–6818 (2018).

CAS 
PubMed 

Google Scholar
 

Li, H., You, Y. & Liu, J. Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression. Mol. Med. Rep. 18, 1165–1170 (2018).

CAS 
PubMed 

Google Scholar
 

Weiswald, L. B. et al. Inactivation of the kinase domain of CDK10 prevents tumor growth in a preclinical model of colorectal cancer, and is accompanied by downregulation of Bcl-2. Mol. Cancer Ther. 16, 2292–2303 (2017).

Article 
CAS 
PubMed 

Google Scholar
 

Windpassinger, C. et al. CDK10 mutations in humans and mice cause severe growth retardation, spine malformations, and developmental delays. Am. J. Hum. Genet. 101, 391–403 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Guen, V. J. et al. A homozygous deleterious CDK10 mutation in a patient with agenesis of corpus callosum, retinopathy, and deafness. Am. J. Med. Genet. A 176, 92–98 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Gu, S. S. et al. Therapeutically increasing MHC-I expression potentiates immune checkpoint blockade. Cancer Discov. 11, 1524–1541 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Manguso, R. T. et al. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547, 413–418 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Belnap, L. P., Cleveland, P. H., Colmerauer, M. E., Barone, R. M. & Pilch, Y. H. Immunogenicity of chemically induced murine colon cancers. Cancer Res. 39, 1174–1179 (1979).

CAS 
PubMed 

Google Scholar
 

Wang, X. et al. In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target. Cell 184, 5357–5374 e5322 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Guo, E. et al. WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway. J. Exp. Med. https://doi.org/10.1084/jem.20210789 (2022).

Bell, H. N. & Zou, W. Beyond the barrier: unraveling the mechanisms of immunotherapy resistance. Annu. Rev. Immunol. 42, 521–550 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Della Corte, C. M. & Byers, L. A. Evading the STING: LKB1 loss leads to STING silencing and immune escape in KRAS-mutant lung cancers. Cancer Discov. 9, 16–18 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Zulato, E. et al. LKB1 loss is associated with glutathione deficiency under oxidative stress and sensitivity of cancer cells to cytotoxic drugs and γ-irradiation. Biochem. Pharmacol. 156, 479–490 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Skoulidis, F. et al. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 635, 462–471 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Zhang, L. et al. Single-cell analyses inform mechanisms of myeloid-targeted therapies in colon cancer. Cell 181, 442–459 e429 (2020).

Article 
CAS 
PubMed 

Google Scholar
 

Dexter, D. L. et al. Heterogeneity of cancer cells from a single human colon carcinoma. Am. J. Med. 71, 949–956 (1981).

Article 
CAS 
PubMed 

Google Scholar
 

van den Heuvel, S. & Harlow, E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science 262, 2050–2054 (1993).

Article 
PubMed 

Google Scholar
 

Robert, T. et al. Development of a CDK10/CycM in vitro kinase screening assay and identification of first small-molecule inhibitors. Front. Chem. 8, 147 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Brown, N. R., Noble, M. E., Endicott, J. A. & Johnson, L. N. The structural basis for specificity of substrate and recruitment peptides for cyclin-dependent kinases. Nat. Cell Biol. 1, 438–443 (1999).

Article 
CAS 
PubMed 

Google Scholar
 

Zhou, X. et al. Pharmacologic activation of p53 triggers viral mimicry response thereby abolishing tumor immune evasion and promoting antitumor immunity. Cancer Discov. 11, 3090–3105 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Takeuchi, O. & Akira, S. Pattern recognition receptors and inflammation. Cell 140, 805–820 (2010).

Article 
CAS 
PubMed 

Google Scholar
 

Crossley, M. P. et al. R-loop-derived cytoplasmic RNA-DNA hybrids activate an immune response. Nature 613, 187–194 (2023).

Article 
CAS 
PubMed 

Google Scholar
 

Yasuhara, T. et al. RAP80 suppresses the vulnerability of R-loops during DNA double-strand break repair. Cell Rep. 38, 110335 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Valk, E., Ord, M., Faustova, I. & Loog, M. CDK signaling via nonconventional CDK phosphorylation sites. Mol. Biol. Cell 34, pe5 (2023).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kusubata, M. et al. cdc2 kinase phosphorylation of desmin at three serine/threonine residues in the amino-terminal head domain. Biochem. Biophys. Res. Commun. 190, 927–934 (1993).

Article 
CAS 
PubMed 

Google Scholar
 

Li, Z. et al. Synthesis and structure-activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold. Eur. J. Med. Chem. 238, 114433 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Duster, R., Ji, Y., Pan, K. T., Urlaub, H. & Geyer, M. Functional characterization of the human Cdk10/Cyclin Q complex. Open Biol. 12, 210381 (2022).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Sachs, R. E., Ginsburg, P. B. & Goldman, D. P. Encouraging new uses for old drugs. JAMA 318, 2421–2422 (2017).

Article 
PubMed 

Google Scholar
 

Weisberg, E. et al. Antileukemic effects of the novel, mutant FLT3 inhibitor NVP-AST487: effects on PKC412-sensitive and -resistant FLT3-expressing cells. Blood 112, 5161–5170 (2008).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kantarjian, H. M. et al. ponatinib-review of historical development, current status, and future research. Am. J. Hematol. 99, 1576–1585 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Eide, C. A. et al. Overcoming clinical BCR-ABL1 compound mutant resistance with combined ponatinib and asciminib therapy. Cancer Cell 42, 1486–1488 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Li, H. et al. USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy. Proc. Natl Acad. Sci. USA 121, e2315541121 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Doench, J. G. et al. Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9. Nat. Biotechnol. 34, 184–191 (2016).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Dai, P. et al. USP2 inhibition unleashes CD47-restrained phagocytosis and enhances anti-tumor immunity. Nat. Commun. 16, 4564 (2025).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Crossley, M. P. et al. Catalytically inactive, purified RNase H1: a specific and sensitive probe for RNA-DNA hybrid imaging. J. Cell Biol. https://doi.org/10.1083/jcb.202101092 (2021).

Zhang, J. et al. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 553, 91–95 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Jiang, P. et al. Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat. Med. 24, 1550–1558 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Mariathasan, S. et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 554, 544–548 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Zhao, J. et al. Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma. Nat. Med. 25, 462–469 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hugo, W. et al. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 165, 35–44 (2016).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Van Allen, E. M. et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350, 207–211 (2015).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Nathanson, T. et al. Somatic mutations and neoepitope homology in melanomas treated with CTLA-4 blockade. Cancer Immunol. Res. 5, 84–91 (2017).

Article 
CAS 
PubMed 

Google Scholar
 

Gong, L. et al. Cancer immunology data engine reveals secreted AOAH as a potential immunotherapy. Cell 188, 5062–5080 e5032 (2025).

Article 
CAS 
PubMed 

Google Scholar
 

Patil, N. S. et al. Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer. Cancer Cell 40, 289–300 e284 (2022).

Article 
CAS 
PubMed 

Google Scholar