{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:23:48Z","timestamp":1792023828614,"version":"4.4.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:00:00Z","timestamp":1717459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Qinghai Provincial Central Guidance Local Science and Technology Development Fund","award":["No. 2022ZY009"],"award-info":[{"award-number":["No. 2022ZY009"]}]},{"name":"Qinghai Provincial Central Guidance Local Science and Technology Development Fund","award":["No. 2022ZY009"],"award-info":[{"award-number":["No. 2022ZY009"]}]},{"name":"Provincial-Level Clinical Key Specialty Construction in Qinghai Province"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cancer Res Clin Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Granzyme K (GZMK) is a crucial mediator released by immune cells to eliminate tumor cells, playing significant roles in inflammation and tumorigenesis. Despite its importance, the specific role of GZMK in breast cancer and its mechanisms are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized data from the TCGA and GEO databases and employed a range of analytical methods including GO, KEGG, GSEA, ssGSEA, and PPI to investigate the impact of GZMK on breast cancer. In vitro studies, including RT-qPCR, CCK-8 assay, cell cycle experiments, apoptosis assays, Celigo scratch assays, Transwell assays, and immunohistochemical methods, were conducted to validate the effects of GZMK on breast cancer cells. Additionally, Cox regression analysis integrating TCGA and our clinical data was used to develop an overall survival (OS) prediction model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of clinical pathological features revealed significant correlations between GZMK expression and lymph node staging, differentiation grade, and molecular breast cancer subtypes. High GZMK expression was associated with improved OS, progression-free survival (PFS), and recurrence-free survival (RFS), as confirmed by multifactorial Cox regression analysis. Functional and pathway enrichment analyses of genes positively correlated with GZMK highlighted involvement in lymphocyte differentiation, T cell differentiation, and T cell receptor signaling pathways. A robust association between GZMK expression and T cell presence was noted in the breast cancer tumor microenvironment (TME), with strong correlations with ESTIMATEScore (Cor\u2009=\u20090.743,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), ImmuneScore (Cor\u2009=\u20090.802,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), and StromalScore (Cor\u2009=\u20090.516,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). GZMK also showed significant correlations with immune checkpoint molecules, including CTLA4 (Cor\u2009=\u20090.856,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), PD-1 (Cor\u2009=\u20090.82,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), PD-L1 (Cor\u2009=\u20090.56,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), CD48 (Cor\u2009=\u20090.75,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), and CCR7 (Cor\u2009=\u20090.856,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Studies indicated that high GZMK expression enhances patient responsiveness to immunotherapy, with higher levels observed in responsive patients compared to non-responsive ones. In vitro experiments confirmed that GZMK promotes cell proliferation, cell division, apoptosis, cell migration, and invasiveness (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides insights into the differential expression of GZMK in breast cancer and its potential mechanisms in breast cancer pathogenesis. Elevated GZMK expression is associated with improved OS and RFS, suggesting its potential as a prognostic marker for breast cancer survival and as a predictor of the efficacy of immunotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00432-024-05791-6","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T06:29:28Z","timestamp":1717482568000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Exploring GZMK as a prognostic marker and predictor of immunotherapy response in breast cancer: unveiling novel insights into treatment outcomes"],"prefix":"10.1007","volume":"150","author":[{"given":"Zitao","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuxing","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinfa","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengfeng","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhilin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshuang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuda","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,4]]},"reference":[{"issue":"6","key":"5791_CR1","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1016\/j.jaci.2022.10.007","volume":"150","author":"I Agache","year":"2022","unstructured":"Agache I, Zemelka-Wi\u0105cek M, Shamji MH et al (2022) Immunotherapy: state-of-the-art review of therapies and theratypes. J Allergy Clin Immunol 150(6):1279\u20131288","journal-title":"J Allergy Clin Immunol"},{"issue":"10","key":"5791_CR2","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1002\/eji.200526249","volume":"35","author":"B Bade","year":"2005","unstructured":"Bade B, Lohrmann J, Ten Brinke A et al (2005) Detection of soluble human granzyme Kin vitro andin vivo. Eur J Immunol 35(10):2940\u20132948","journal-title":"Eur J Immunol"},{"issue":"2","key":"5791_CR3","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.ccell.2023.12.005","volume":"42","author":"M Benguigui","year":"2024","unstructured":"Benguigui M, Cooper TJ, Kalkar P et al (2024) Interferon-stimulated neutrophils as a predictor of immunotherapy response. Cancer Cell 42(2):253-265.e12","journal-title":"Cancer Cell"},{"issue":"10","key":"5791_CR4","doi-asserted-by":"publisher","first-page":"e463","DOI":"10.1016\/S1470-2045(20)30328-4","volume":"21","author":"S Billan","year":"2020","unstructured":"Billan S, Kaidar-Person O, Gil Z (2020) Treatment after progression in the era of immunotherapy. Lancet Oncol 21(10):e463\u2013e476","journal-title":"Lancet Oncol"},{"issue":"4","key":"5791_CR5","doi-asserted-by":"publisher","first-page":"100502","DOI":"10.1016\/j.esmoop.2022.100502","volume":"7","author":"C Blaye","year":"2022","unstructured":"Blaye C, Darbo \u00c9, Debled M et al (2022) An immunological signature to predict outcome in patients with triple-negative breast cancer with residual disease after neoadjuvant chemotherapy. ESMO Open 7(4):100502","journal-title":"ESMO Open"},{"issue":"24","key":"5791_CR6","doi-asserted-by":"publisher","first-page":"5011","DOI":"10.1242\/jcs.03239","volume":"119","author":"M Bots","year":"2006","unstructured":"Bots M, Medema JP (2006) Granzymes at a glance. J Cell Sci 119(24):5011\u20135014","journal-title":"J Cell Sci"},{"key":"5791_CR7","doi-asserted-by":"publisher","first-page":"677707","DOI":"10.3389\/fimmu.2021.677707","volume":"12","author":"AC Bouwman","year":"2021","unstructured":"Bouwman AC, Van Daalen KR, Crnko S et al (2021) Intracellular and extracellular roles of granzyme K. Front Immunol 12:677707","journal-title":"Front Immunol"},{"issue":"1","key":"5791_CR8","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/j.0105-2896.2010.00889.x","volume":"235","author":"N Bovenschen","year":"2010","unstructured":"Bovenschen N, Kummer JA (2010) Orphan granzymes find a home: Orphan granzymes find a home. Immunol Rev 235(1):117\u2013127","journal-title":"Immunol Rev"},{"issue":"6","key":"5791_CR9","doi-asserted-by":"publisher","first-page":"3504","DOI":"10.1074\/jbc.M806716200","volume":"284","author":"N Bovenschen","year":"2009","unstructured":"Bovenschen N, Quadir R, Van Den Berg AL et al (2009) Granzyme K displays highly restricted substrate specificity that only partially overlaps with granzyme A. J Biol Chem 284(6):3504\u20133512","journal-title":"J Biol Chem"},{"issue":"1","key":"5791_CR10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s40364-022-00413-0","volume":"10","author":"H Cai","year":"2022","unstructured":"Cai H, Li M, Deng R et al (2022) Advances in molecular biomarkers research and clinical application progress for gastric cancer immunotherapy. Biomarker Research 10(1):67","journal-title":"Biomarker Research"},{"key":"5791_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.12.008","author":"CD Camell","year":"2020","unstructured":"Camell CD (2020) Taa Cells and Granzyme K: Old Players with New Tricks. Immunity. https:\/\/doi.org\/10.1016\/j.immuni.2020.12.008","journal-title":"Immunity"},{"issue":"4","key":"5791_CR12","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.immuni.2007.08.014","volume":"27","author":"X Cao","year":"2007","unstructured":"Cao X, Cai SF, Fehniger TA et al (2007) Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 27(4):635\u2013646","journal-title":"Immunity"},{"issue":"6","key":"5791_CR13","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/s41571-021-00473-5","volume":"18","author":"DB Doroshow","year":"2021","unstructured":"Doroshow DB, Bhalla S, Beasley MB et al (2021) PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol 18(6):345\u2013362","journal-title":"Nat Rev Clin Oncol"},{"issue":"8","key":"5791_CR14","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.annonc.2021.05.355","volume":"32","author":"LA Emens","year":"2021","unstructured":"Emens LA, Adams S, Barrios CH et al (2021) First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis. Ann Oncol 32(8):983\u2013993","journal-title":"Ann Oncol"},{"issue":"5","key":"5791_CR15","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1016\/j.annonc.2022.02.004","volume":"33","author":"L Gianni","year":"2022","unstructured":"Gianni L, Huang CS, Egle D et al (2022) Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann Oncol 33(5):534\u2013543","journal-title":"Ann Oncol"},{"issue":"8","key":"5791_CR16","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1016\/j.molimm.2007.11.020","volume":"45","author":"Y Guo","year":"2008","unstructured":"Guo Y, Chen J, Zhao T et al (2008) Granzyme K degrades the redox\/DNA repair enzyme Ape1 to trigger oxidative stress of target cells leading to cytotoxicity. Mol Immunol 45(8):2225\u20132235","journal-title":"Mol Immunol"},{"issue":"9","key":"5791_CR17","doi-asserted-by":"publisher","first-page":"5348","DOI":"10.4049\/jimmunol.0903792","volume":"185","author":"Y Guo","year":"2010","unstructured":"Guo Y, Chen J, Shi L et al (2010) Valosin-containing protein cleavage by granzyme k accelerates an endoplasmic reticulum stress leading to caspase-independent cytotoxicity of target tumor cells. J Immunol 185(9):5348\u20135359","journal-title":"J Immunol"},{"issue":"2","key":"5791_CR18","doi-asserted-by":"publisher","first-page":"126","DOI":"10.5582\/bst.8.126","volume":"8","author":"Y Hirata","year":"2014","unstructured":"Hirata Y, Inagaki H, Shimizu T et al (2014) Substrate specificity of human granzyme 3: Analyses of the P3-P2-P1 triplet using fluorescence resonance energy transfer substrate libraries. Biosci Trends 8(2):126\u2013131","journal-title":"Biosci Trends"},{"issue":"4","key":"5791_CR19","doi-asserted-by":"publisher","first-page":"2152","DOI":"10.4049\/jimmunol.0802307","volume":"182","author":"G Hua","year":"2009","unstructured":"Hua G, Wang S, Zhong C et al (2009) Ignition of p53 bomb sensitizes tumor cells to granzyme K-Mediated Cytolysis. J Immunol 182(4):2152\u20132159","journal-title":"J Immunol"},{"key":"5791_CR20","first-page":"213","volume":"15","author":"Q Huo","year":"2023","unstructured":"Huo Q, Ning L, Xie N (2023) Identification of GZMA as a potential therapeutic target involved in immune infiltration in breast cancer by integrated bioinformatical analysis. Breast Cancer 15:213\u2013226","journal-title":"Breast Cancer"},{"issue":"2","key":"5791_CR21","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.ccell.2020.10.001","volume":"39","author":"DL Jardim","year":"2021","unstructured":"Jardim DL, Goodman A, De Melo GD et al (2021) The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell 39(2):154\u2013173","journal-title":"Cancer Cell"},{"issue":"3","key":"5791_CR22","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1089\/vim.2008.0036","volume":"21","author":"MR Jenkins","year":"2008","unstructured":"Jenkins MR, Trapani JA, Doherty PC et al (2008) Granzyme K Expressing Cytotoxic T Lymphocytes Protects Against Influenza Virus in Granzyme AB \u2212\/\u2212 Mice. Viral Immunol 21(3):341\u2013346","journal-title":"Viral Immunol"},{"key":"5791_CR23","doi-asserted-by":"publisher","first-page":"1060308","DOI":"10.3389\/fimmu.2023.1060308","volume":"14","author":"M Khan","year":"2023","unstructured":"Khan M, Du K, Ai M et al (2023) PD-L1 expression as biomarker of efficacy of PD-1\/PD-L1 checkpoint inhibitors in metastatic triple negative breast cancer: A systematic review and meta-analysis. Front Immunol 14:1060308","journal-title":"Front Immunol"},{"issue":"4","key":"5791_CR24","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.4110\/in.2023.23.e35","volume":"23","author":"YJ Kim","year":"2023","unstructured":"Kim YJ, Rho KN, Jeong S et al (2023) CD5 expression dynamically changes during the differentiation of human CD8 + T cells predicting clinical response to immunotherapy. Immune Network 23(4):e35","journal-title":"Immune Network"},{"issue":"5","key":"5791_CR25","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1182\/blood-2004-06-2180","volume":"105","author":"FC Kurschus","year":"2005","unstructured":"Kurschus FC, Bruno R, Fellows E et al (2005) Membrane receptors are not required to deliver granzyme B during killer cell attack. Blood 105(5):2049\u20132058","journal-title":"Blood"},{"issue":"5","key":"5791_CR26","doi-asserted-by":"publisher","first-page":"e387","DOI":"10.1002\/mco2.387","volume":"4","author":"X Lin","year":"2023","unstructured":"Lin X, Zong C, Zhang Z et al (2023) Progresses in biomarkers for cancer immunotherapy. MedComm 4(5):e387","journal-title":"MedComm"},{"issue":"6491","key":"5791_CR27","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/370650a0","volume":"370","author":"B Lowin","year":"1994","unstructured":"Lowin B, Hahne M, Mattmann C et al (1994) Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370(6491):650\u2013652","journal-title":"Nature"},{"issue":"1","key":"5791_CR28","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12916-019-1326-5","volume":"17","author":"A Marra","year":"2019","unstructured":"Marra A, Viale G, Curigliano G (2019) Recent advances in triple negative breast cancer: the immunotherapy era. BMC Med 17(1):90","journal-title":"BMC Med"},{"issue":"10278","key":"5791_CR29","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1016\/S0140-6736(20)32598-8","volume":"397","author":"F Meric-Bernstam","year":"2021","unstructured":"Meric-Bernstam F, Larkin J, Tabernero J et al (2021) Enhancing anti-tumour efficacy with immunotherapy combinations. The Lancet 397(10278):1010\u20131022","journal-title":"The Lancet"},{"issue":"18","key":"5791_CR30","doi-asserted-by":"publisher","first-page":"4456","DOI":"10.3390\/cancers15184456","volume":"15","author":"K Mizoguchi","year":"2023","unstructured":"Mizoguchi K, Kawaji H, Kai M et al (2023) Granzyme B expression in the tumor microenvironment as a prognostic biomarker for patients with triple-negative breast cancer. Cancers 15(18):4456","journal-title":"Cancers"},{"issue":"8","key":"5791_CR31","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1016\/j.cell.2023.01.040","volume":"186","author":"E Nolan","year":"2023","unstructured":"Nolan E, Lindeman GJ, Visvader JE (2023) Deciphering breast cancer: from biology to the clinic. Cell 186(8):1708\u20131728","journal-title":"Cell"},{"issue":"1","key":"5791_CR32","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.molmed.2014.10.009","volume":"21","author":"KC Ohaegbulam","year":"2015","unstructured":"Ohaegbulam KC, Assal A, Lazar-Molnar E et al (2015) Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med 21(1):24\u201333","journal-title":"Trends Mol Med"},{"issue":"9","key":"5791_CR33","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1056\/NEJMoa1910549","volume":"382","author":"P Schmid","year":"2020","unstructured":"Schmid P, Cortes J, Pusztai L et al (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382(9):810\u2013821","journal-title":"N Engl J Med"},{"issue":"1","key":"5791_CR34","first-page":"12","volume":"74","author":"RL Siegel","year":"2024","unstructured":"Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA 74(1):12\u201349","journal-title":"CA"},{"key":"5791_CR35","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.canlet.2017.11.014","volume":"414","author":"F Teng","year":"2018","unstructured":"Teng F, Meng X, Kong L et al (2018) Progress and challenges of predictive biomarkers of anti PD-1\/PD-L1 immunotherapy: A systematic review. Cancer Lett 414:166\u2013173","journal-title":"Cancer Lett"},{"issue":"1","key":"5791_CR36","doi-asserted-by":"publisher","first-page":"6752","DOI":"10.1038\/s41467-022-34467-3","volume":"13","author":"S Tiberti","year":"2022","unstructured":"Tiberti S, Catozzi C, Croci O et al (2022) GZMKhigh CD8+ T effector memory cells are associated with CD15high neutrophil abundance in non-metastatic colorectal tumors and predict poor clinical outcome. Nat Commun 13(1):6752","journal-title":"Nat Commun"},{"issue":"6477","key":"5791_CR37","doi-asserted-by":"publisher","first-page":"eaax0182","DOI":"10.1126\/science.aax0182","volume":"367","author":"SL Topalian","year":"2020","unstructured":"Topalian SL, Taube JM, Pardoll DM (2020) Neoadjuvant checkpoint blockade for cancer immunotherapy. Science 367(6477):eaax0182","journal-title":"Science"},{"key":"5791_CR38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1074\/jbc.M112.365692","volume":"287","author":"R van Domselaar","year":"2012","unstructured":"van Domselaar R, Quadir R (2012) All Human Granzymes Target hnRNP K That Is Essential for Tumor Cell Viability. J Biol Chem 287:27","journal-title":"J Biol Chem"},{"issue":"3","key":"5791_CR39","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","volume":"2","author":"T Wu","year":"2021","unstructured":"Wu T, Hu E, Xu S et al (2021a) Clusterprofiler 4.0: A universal enrichment tool for interpreting omics data. The Innovation 2(3):100141","journal-title":"The Innovation"},{"issue":"7","key":"5791_CR40","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.7150\/ijms.54747","volume":"18","author":"X Wu","year":"2021","unstructured":"Wu X, Wang X, Zhao Y et al (2021b) Granzyme family acts as a predict biomarker in cutaneous melanoma and indicates more benefit from anti-PD-1 immunotherapy. Int J Med Sci 18(7):1657\u20131669","journal-title":"Int J Med Sci"},{"issue":"1","key":"5791_CR41","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s13045-022-01242-2","volume":"15","author":"M Wu","year":"2022","unstructured":"Wu M, Huang Q, Xie Y et al (2022) Improvement of the anticancer efficacy of PD-1\/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol 15(1):24","journal-title":"J Hematol Oncol"},{"issue":"6","key":"5791_CR42","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.1158\/2159-8290.CD-20-1209","volume":"11","author":"TA Yap","year":"2021","unstructured":"Yap TA, Parkes EE, Peng W et al (2021) Development of Immunotherapy Combination Strategies in Cancer. Cancer Discov 11(6):1368\u20131397","journal-title":"Cancer Discov"},{"issue":"12","key":"5791_CR43","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/j.ccell.2021.09.010","volume":"39","author":"Y Zhang","year":"2021","unstructured":"Zhang Y, Chen H, Mo H et al (2021) Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer. Cancer Cell 39(12):1578-1593.e8","journal-title":"Cancer Cell"},{"key":"5791_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4402040","author":"T Zhao","year":"2007","unstructured":"Zhao T, Zhang H, Guo Y et al (2007a) Granzyme K cleaves the nucleosome assembly protein SET to induce single-stranded DNA nicks of target cells. Cell Death Differ. https:\/\/doi.org\/10.1038\/sj.cdd.4402040","journal-title":"Cell Death Differ"},{"issue":"16","key":"5791_CR45","doi-asserted-by":"publisher","first-page":"12104","DOI":"10.1074\/jbc.M611006200","volume":"282","author":"T Zhao","year":"2007","unstructured":"Zhao T, Zhang H, Guo Y et al (2007b) Granzyme K Directly processes bid to release cytochrome c and endonuclease G leading to mitochondria-dependent cell death. J Biol Chem 282(16):12104\u201312111","journal-title":"J Biol Chem"}],"container-title":["Journal of Cancer Research and Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05791-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00432-024-05791-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00432-024-05791-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T06:51:33Z","timestamp":1720507893000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00432-024-05791-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,4]]},"references-count":45,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["5791"],"URL":"https:\/\/doi.org\/10.1007\/s00432-024-05791-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4004163\/v1","asserted-by":"object"}]},"ISSN":["1432-1335"],"issn-type":[{"value":"1432-1335","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,4]]},"assertion":[{"value":"1 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 June 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}],"article-number":"286"}}