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While immunotherapy markedly improves outcomes for many patients, clinical evidence indicates that non\u2013small\u2010cell lung cancer (NSCLC) patients with elevated Aurora A expression exhibit reduced therapeutic responses to immune checkpoint blockade. Elucidating the underlying mechanisms may unlock novel strategies to enhance the clinical benefits for this subset. In this study, we characterised cellular senescence and tumour microenvironment interactions using lung cancer cell lines with different Aurora A expression levels. H23 (high Aurora A expression) and A549 (low Aurora A expression) cells were selected to model tumour\u2010immune crosstalk. Tumour\u2010infiltrating lymphocytes (TILs) were isolated and activated via anti\u2010CD28 costimulation. Through gain\u2010 and loss\u2010of\u2010function experiments, we established the optimal conditions to induce T\u2010lymphocyte apoptosis and identified critical cell ratios and culture durations. In these co\u2010culture systems, immune checkpoint inhibitors more effectively suppressed Aurora A\u2010low tumour growth. Mechanistically, Aurora A overexpression exacerbated T\u2010lymphocyte apoptosis via the NOXA\u2010MCL\u20101 pathway. Further analysis revealed that Aurora A disrupts the eIF4G:eIF4E complex by suppressing p4E\u2010BP1, thereby up\u2010regulating the pro\u2010apoptotic factor NOXA while down\u2010regulating the anti\u2010apoptotic factor MCL\u20101. Aurora A\u2010driven T\u2010lymphocyte apoptosis via the NOXA\u2010MCL\u20101 axis compromises PD\u20101\/PD\u2010L1\u2010mediated immune responses, providing a molecular rationale for immunotherapy resistance in Aurora A\u2010high NSCLC patients. Targeting this pathway may restore T\u2010cell viability and improve therapeutic outcomes.<\/jats:p>","DOI":"10.1111\/1440-1681.70132","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:15:02Z","timestamp":1779930902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aurora A\u2010Mediated Exosomal Secretion of\n                    <scp>miR<\/scp>\n                    \u2010644a Promotes T\u2010Lymphocyte Apoptosis Through the\n                    <scp>NOXA<\/scp>\n                    \/\n                    <scp>p4E<\/scp>\n                    \u2010\n                    <scp>BP1<\/scp>\n                    \/\n                    <scp>MCL<\/scp>\n                    \u20101 Pathway"],"prefix":"10.1111","volume":"53","author":[{"given":"Ziyi","family":"Zhou","sequence":"first","affiliation":[{"name":"The 1st Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Chen","sequence":"additional","affiliation":[{"name":"Inner Mongolia People's Hospital, Baotou Medical College Inner Mongolia University of Science&amp; Technology  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Zheng","sequence":"additional","affiliation":[{"name":"The 1st Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewen","family":"Wan","sequence":"additional","affiliation":[{"name":"Jiujiang No. 1 People's Hospital  Jiujiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Kuang","sequence":"additional","affiliation":[{"name":"The 1st Affiliated Hospital, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.07.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v9.i21.5782"},{"key":"e_1_2_9_4_1","volume-title":"Lung Cancer Overview and Therapies","author":"Abhishek Tiwari V. 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