1. Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial.
作者: Jean E Abraham.;Lenka Oplustil O'Connor.;Louise Grybowicz.;Karen Pinilla Alba.;Alimu Dayimu.;Nikolaos Demiris.;Caron Harvey.;Lynsey M Drewett.;Rebecca Lucey.;Alexander Fulton.;Anne N Roberts.;Joanna R Worley.;Ms Anita Chhabra.;Wendi Qian.;Jessica Brown.;Richard Hardy.;Anne-Laure Vallier.;Steve Chan.;Maria Esther Una Cidon.;Elizabeth Sherwin.;Amitabha Chakrabarti.;Claire Sadler.;Jen Barnes.;Mojca Persic.;Sarah Smith.;Sanjay Raj.;Annabel Borley.;Jeremy P Braybrooke.;Emma Staples.;Lucy C Scott.;Cheryl A Palmer.;Margaret Moody.;Mark J Churn.;Domenic Pilger.;Guido Zagnoli-Vieira.;Paul W G Wijnhoven.;Mukesh B Mukesh.;Rebecca R Roylance.;Philip C Schouten.;Nicola C Levitt.;Karen McAdam.;Anne C Armstrong.;Ellen R Copson.;Emma McMurtry.;Susan Galbraith.;Marc Tischkowitz.;Elena Provenzano.;Mark J O'Connor.;Helena M Earl.; .
来源: Nat Commun. 2025年16卷1期4269页
Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.
2. Idarubicin versus Epirubicin in Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage B Hepatocellular Carcinoma: An Open-label, Randomized, Phase IV Trial.
作者: Haikuan Liu.;Wenzhe Fan.;Haiqing Li.;Liangliang Qiao.;Zhilong Liu.;Bowen Zhu.;Jian Guo.;Kun Huang.;Yiyang Tang.;Jie Wen.;Miao Xue.;Yanqin Wu.;Yue Zhao.;Yang Jiang.;Kangshou Liu.;Junjie Liang.;Mingrong Cao.;Jiaping Li.
来源: Radiology. 2025年315卷2期e242315页
Background Transarterial chemoembolization (TACE) is regarded as the first-line treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC). However, the optimal chemotherapeutic agent loaded in TACE remains controversial. Purpose To compare the efficacy and safety of idarubicin and epirubicin as loaded drugs in drug-eluting bead (DEB)-TACE in patients with BCLC stage B HCC. Materials and Methods In this open-label, phase IV trial, patients with BCLC stage B HCC were recruited from four centers from August 2020 to October 2022 and randomly assigned (at a one-to-one ratio) to undergo idarubicin DEB-TACE or epirubicin DEB-TACE. The primary end point was progression-free survival (PFS), which was measured from the time of randomization to the time of progression or death from any cause. The efficacy analysis was conducted on an intention-to-treat basis, and only participants who received treatment were included in the safety analysis. Results A total of 239 participants (median age, 57 years; IQR, 50-66 years; 210 male) were randomly assigned to the idarubicin group (n = 120) or the epirubicin group (n = 119). The primary analysis cutoff for PFS was March 1, 2023, with 167 events observed (70%; idarubicin group, 85 events; epirubicin group, 82 events). The median PFS was 10.8 months and 8.7 months in the idarubicin and epirubicin groups, respectively (hazard ratio [HR], 0.61; 95% CI: 0.44, 0.84; P = .002). The HR for median overall survival (OS) was 0.53 (95% CI: 0.31, 0.88), with OS rates of 81.5% and 77.3% at 12 months and 71.8% and 54.0% at 24 months for the idarubicin and epirubicin groups, respectively. The objective response rates were 70.8% and 57.1% for the idarubicin and epirubicin groups, respectively (P = .03). There was no evidence of a between-group difference in incidence of adverse events, including hematologic toxicity. No treatment-related deaths were observed. Conclusion Idarubicin DEB-TACE increased survival in participants with BCLC stage B HCC, without an increase in the incidence of any adverse events. Clinical trial registration no. ChiCTR2000034758 © RSNA, 2025 Supplemental material is available for this article.
3. Cemiplimab monotherapy as first-line treatment of patients with brain metastases from advanced non-small cell lung cancer with programmed cell death-ligand 1 ≥50.
作者: Saadettin Kilickap.;Mustafa Özgüroğlu.;Ahmet Sezer.;Mahmut Gümüş.;Igor Bondarenko.;Miranda Gogishvili.;Haci M Turk.;Irfan Cicin.;Dmitry Bentsion.;Oleg Gladkov.;Virote Sriuranpong.;Ruben G W Quek.;Debra A G McIntyre.;Xuanyao He.;Jennifer McGinniss.;Frank Seebach.;Giuseppe Gullo.;Petra Rietschel.;Jean-Francois Pouliot.
来源: Cancer. 2025年131卷10期e35864页
In the phase 3 EMPOWER-Lung 1 study, first-line cemiplimab monotherapy provided significant survival benefit versus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. This exploratory subgroup analysis investigated the clinical outcomes of cemiplimab treatment in patients with advanced NSCLC with brain metastases.
4. Early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumour burden follicular lymphoma: long-term results of a randomised, phase 3 trial.
作者: Michael Northend.;William Wilson.;Kushani Ediriwickrema.;Laura Clifton-Hadley.;Wendi Qian.;Zaynab Rana.;Tanya-Louise Martin.;William Townsend.;Moya Young.;Fiona Miall.;David Cunningham.;Jan Walewski.;Burhan Ferhanoglu.;Kim Linton.;Amanda Johnston.;John F Seymour.;David C Linch.;Kirit M Ardeshna.
来源: Lancet Haematol. 2025年12卷5期e335-e345页
Initial results of this study, reported after a median follow-up close to 4 years, demonstrated improved time to initiation of new treatment (TTNT) for patients with advanced stage, asymptomatic, low tumour burden follicular lymphoma who received early rituximab monotherapy when compared with watchful waiting. Given the long natural history of follicular lymphoma, the trial was extended to further assess TTNT with longer follow-up. Mature data are presented here.
5. Predictive Effect of IGFBP-3 on Low-Dose Tamoxifen Efficacy in Noninvasive Breast Cancer in the Phase III Tam-01 Trial.
作者: Harriet Johansson.;Debora Macis.;Martino Oliva.;Matteo Puntoni.;Eva Blondeaux.;Aliana Guerrieri-Gonzaga.;Valentina Aristarco.;Irene Maria Briata.;Tania Buttiron-Webber.;Luca Boni.;Matteo Lazzeroni.;Davide Serrano.;Livia Giordano.;Maria Digennaro.;Laura Cortesi.;Francesco Millo.;Katia Cagossi.;Giuseppe Aprile.;Fabio Falcini.;Elisa Gallerani.;Bernardo Bonanni.;Andrea DeCensi.
来源: Clin Cancer Res. 2025年31卷10期1841-1846页
Low-dose tamoxifen 5 mg/day (babytam) for 3 years can decrease the incidence of new breast cancer events in women with breast intraepithelial neoplasia by 42% with limited toxicity, which provides a new treatment option for these disorders. However, predictive biomarkers of babytam efficacy are lacking. We studied whether baseline levels of insulin-like growth factor-1 (IGF-I), IGF-binding protein-3 (IGFBP-3), estradiol, and sex hormone-binding globulin (SHBG) and their ratios predict babytam efficacy on breast cancer events in a preplanned secondary analysis.
6. [Phase Ⅲ, multicenter, randomized comparative study of LY01005 and Zoladex® for patients with premenopausal breast cancer].
作者: X Y Shao.;Q Y Zhang.;Z F Niu.;M Li.;J F Wang.;Z Z Chen.;R Z Luo.;G D Qiao.;J G Wang.;L Y Qian.;R H Yang.;Z D Chen.;J Wang.;Y M Yao.;J H Ou.;T Sun.;Q Cheng.;Y S Wang.;J Huang.;H Y Zhao.;W Y Su.;Z Ouyang.;Y Ding.;L L Chen.;S M Yang.;M S Cui.;A M Zang.;E X Zhou.;P Z Fan.;J Zhang.;Q Liu.;Y E Teng.;H Li.;J Y Nie.;J Yang.;X J Wang.;Z F Jiang.
来源: Zhonghua Zhong Liu Za Zhi. 2025年47卷4期340-348页
Background: To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex® in Chinese patients with premenopausal breast cancer. Methods: From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex® every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results: A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex®. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex®. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex® group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion: LY01005 is as effective as Zoladex® in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.
7. Integrating psychological and dietary care for patients with advanced gastric cancer undergoing chemotherapy: a randomized controlled trial.
This study was to investigate the effects of psychological care with dietary care on the psychological state and quality of life of patients undergoing chemotherapy for advanced gastric cancer (GC).
8. Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Long-term follow-up, crossover, and rechallenge with pembrolizumab in the phase III KEYNOTE-716 study.
作者: Jason J Luke.;Paolo A Ascierto.;Muhammad A Khattak.;Piotr Rutkowski.;Michele Del Vecchio.;Francesco Spagnolo.;Jacek Mackiewicz.;Luis de la Cruz Merino.;Vanna Chiarion-Sileni.;John M Kirkwood.;Caroline Robert.;Dirk Schadendorf.;Federica de Galitiis.;Matteo S Carlino.;Reinhard Dummer.;Peter Mohr.;Amos Odeleye-Ajakaye.;Mizuho Fukunaga-Kalabis.;Clemens Krepler.;Alexander M M Eggermont.;Georgina V Long.
来源: Eur J Cancer. 2025年220卷115381页
Adjuvant pembrolizumab prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB/IIC melanoma in KEYNOTE-716. Results of a post hoc 4-year analysis are reported, including progression/recurrence-free survival 2 (PRFS2).
9. Glutamine Mouthwash for Preventing Methotrexate-Induced Mucositis in Children with Acute Lymphoblastic Leukemia: A Randomized Cross-Over Trial.
作者: S Siva Sankaran.;Pooja Dewan.;Rajeev Kumar Malhotra.;Deepika Harit.;Bineeta Kashyap.;Mukesh Yadav.;Mandeep Singh Khalsa.
来源: Indian Pediatr. 2025年62卷4期269-275页
To assess the efficacy of glutamine mouthwash versus standard oral hygiene protocol (SOHP) in reducing the overall incidence, duration and severity of oral mucositis in children with acute lymphoblastic leukemia (ALL) receiving High Dose Methotrexate (HDMTX).
10. High-Dose Methotrexate in Children and Young Adults With ALL and Lymphoblastic Lymphoma: Results of the Randomized Phase III Study UKALL 2011.
作者: Amy A Kirkwood.;Nicholas Goulden.;John Moppett.;Sujith Samarasinghe.;Rachael Hough.;Clare Rowntree.;Sarah Lawson.;Pam Kearns.;Anna Lawson.;Ajay Vora.
来源: J Clin Oncol. 2025年43卷15期1810-1823页
UKALL 2011 randomly assigned children and young adults (younger than 25 years) with ALL or lymphoblastic lymphoma. The aims were to reduce induction toxicity (randomization 1 [R1]), CNS relapse risk (randomization 2 [R2]-interim maintenance [R2IM]), and maintenance morbidity (R2pulses).
11. Quality-Adjusted Time Without Symptoms of Disease or Toxicity (Q-TWiST) in Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Comparison of Ponatinib Versus Imatinib.
作者: Ajibade Ashaye.;Ling Shi.;Ibrahim Aldoss.;Pau Montesinos.;Pankit Vachhani.;Vanderson Rocha.;Cristina Papayannidis.;Jessica T Leonard.;Maria R Baer.;Jose-Maria Ribera.;James McCloskey.;Jianxiang Wang.;Deepali Rane.;Shien Guo.
来源: Cancer Med. 2025年14卷7期e70780页
In the phase 3 ponatinib-3001 trial (PhALLCON, NCT03589326), ponatinib demonstrated superior efficacy over imatinib with comparable safety in patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). This post hoc analysis evaluated the net benefits of ponatinib using a quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) approach.
12. Efficacy of Rikkunshito on Chemotherapy-Induced Nausea and Vomiting in Patients With Uterine Corpus or Cervical Cancer Treated With Cisplatin-Based Regimen-Placebo-controlled, Double-Blind, Randomized Confirmatory Study (JORTC-KMP03).
作者: Yosuke Konno.;Shunsuke Ohnishi.;Shinichiro Minobe.;Eiji Nomura.;Takayuki Nagasawa.;Etsuko Fujimoto.;Tatsuru Ohara.;Shin Nishio.;Hisamori Kato.;Yoshihito Yokoyama.;Etsuko Miyagi.;Hideki Tokunaga.;Koji Nishino.;Akira Kikuchi.;Yoshio Yoshida.;Takashi Iwata.;Daito Noguchi.;Wataru Kudaka.;Shunsuke Oyamada.;Keisuke Ariyoshi.;Kota Kihara.;Hidemichi Watari.
来源: Integr Cancer Ther. 2025年24卷15347354251329346页
The current standard treatment for chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics is insufficient. Rikkunshito, a Japanese traditional herbal medicine, has been shown to improve cisplatin-induced anorexia and functional dyspepsia, and our exploratory study found that rikkunshito has an additive beneficial effect on CINV in patients with uterine corpus and cervical cancer receiving cisplatin containing chemotherapy (JORTC KMP-02).
13. The Effect of Nurse Navigators in Digital Remote Monitoring in Cancer Care: Case Study Using Structural Equation Modeling.
作者: Etienne Minvielle.;Joel Perez-Torrents.;Israa Salma.;Philippe Aegerter.;Marie Ferrua.;Charles Ferté.;Henri Leleu.;Delphine Mathivon.;Claude Sicotte.;Mario Di Palma.;Florian Scotté.
来源: J Med Internet Res. 2025年27卷e66275页
The purpose of digital remote monitoring (DRM) is improving cancer care management. However, its effectiveness largely depends on the role of nurse navigators (NNs) within these systems to process data and lead action.
14. Aflibercept With vs Without Reduced-Fluence Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial.
作者: Yu Jeat Chong.;Kelvin Yi Chong Teo.;Wendy Wong.;Anna C S Tan.;Xinyi Su.;Noa Gilead.;Hiok Hong Chan.;Farah Ibrahim.;Beau Fenner.;Charles Ong.;Christopher Sun.;Shaun Sim.;Caroline Chee.;Usha Chakravarthy.;Chui Ming Gemmy Cheung.
来源: JAMA Ophthalmol. 2025年143卷5期393-399页
The potential benefit of adding photodynamic therapy (PDT) to intravitreal aflibercept injection (IAI) in eyes with polypoidal choroidal vasculopathy (PCV) remains unclear.
15. ENGOT-OV16/NOVA trial of niraparib in recurrent ovarian cancer: Survival and long-term safety.
作者: Ursula A Matulonis.;Jørn Herrstedt.;Amit Oza.;Sven Mahner.;Andrés Redondo.;Dominique Berton.;Jonathan S Berek.;Charlotte A Haslund.;Frederik Marmé.;Antonio González-Martín.;Stéphanie Bécourt.;Anna V Tinker.;Jonathan A Ledermann.;Benedict Benigno.;Gabriel Lindahl.;Nicoletta Colombo.;Izabela A Malinowska.;Wenlei Liu.;Manjinder Bains.;Bradley J Monk.;Mansoor R Mirza.
来源: Gynecol Oncol. 2025年195卷192-199页
To evaluate secondary efficacy endpoints and safety for the ENGOT-OV16/NOVA (NCT01847274) trial of niraparib maintenance therapy after extended follow-up and vital-status-data retrieval. Previously reported analyses (data cutoff, October 1, 2020) indicated benefit of niraparib maintenance therapy beyond first progression, but overall survival (OS) analyses were limited by missing data.
16. Patient-reported outcomes with adjuvant nivolumab versus placebo after complete resection of stage IIB/C melanoma in the randomized phase 3 CheckMate 76 K trial.
作者: John M Kirkwood.;Peter Mohr.;Christoph Hoeller.;Jean-Jacques Grob.;Michele Del Vecchio.;Jennifer Lord-Bessen.;Swetha Srinivasan.;Ayman Nassar.;Federico Campigotto.;Hannah Fairbanks.;Fiona Taylor.;Rachael Lawrance.;Georgina V Long.;Jeffrey Weber.
来源: Eur J Cancer. 2025年220卷115371页
In the phase 3 CheckMate 76 K trial, adjuvant nivolumab significantly improved recurrence-free survival and distant metastasis-free survival versus placebo in patients with resected stage IIB/C melanoma. We report patient-reported outcomes from CheckMate 76 K.
17. Effect of honey-ginger mouthwash on oral mucositis in patients undergoing chemotherapy.
作者: Fatemeh Sadat Razavi.;Hania Zokaee.;Mojtaba Sehat.;Mohsen Taghizadeh.;Hossein Motedayyen.;Elaheh Ghasemzadeh Hoseini.
来源: J Immunoassay Immunochem. 2025年46卷3期303-315页
Oral mucositis is considered as one of the most prevalent complications of chemotherapy or radiation therapy in cancerous tumors, which can interrupt the patient's treatment and nutrition. This study therefore aimed to evaluate the efficacy of ginger-honey mouthwash on the prevention of chemotherapy-induced oral mucositis in patients suffering from various cancers.
18. Feasibility and Safety of Intratympanic Administration of Sustained-Exposure Dexamethasone Thermosensitive Gel (OTO-104) for Prevention of Cisplatin-Induced Hearing Loss in Children: A Multisite Phase 2 Randomized Clinical Trial.
作者: David R Freyer.;Timothy J D Ohlsen.;Debra Don.;Etan Orgel.;Robert J Hayashi.;Judith E Lieu.;Jennifer H Foster.;Matthew S Sitton.;James I Geller.;Daniel I Choo.;Arun Rangaswami.;Kay W Chang.;Brian Greffe.;Kenny Chan.;Alice Lee.;Eli Grunstein.;Allison F O'Neill.;Reza Rahbar.;Jeffery J Anderson.
来源: Pediatr Blood Cancer. 2025年72卷6期e31680页
Cisplatin-induced hearing loss (CIHL) remains a significant complication of pediatric cancer treatment. We evaluated the feasibility, safety, and trends of the efficacy of intratympanic injections of sustained-exposure dexamethasone thermosensitive gel (OTO-104) for otoprotection.
19. Olanzapine Versus NK1 Receptor Antagonist for Prevention of Carboplatin-Induced (AUC ≥4) Emesis: A Phase III, Double-Blind, Placebo-Controlled Randomized Trial From India.
作者: Sneh Bhargave.;Vinod Sharma.;Babita Kataria.;Atul Batra.;Deepam Pushpam.;Aparna Sharma.;Raja Pramanik.;Prabhat S Malik.;Ranjit K Sahoo.;Sachin Khurana.;Vishwajeet Singh.;Sameer Bakhshi.;Atul Sharma.;Lalit Kumar.;Akash Kumar.
来源: JCO Glob Oncol. 2025年11卷e2400166页
Prevention of chemotherapy-induced nausea and vomiting with currently recommended NK1 receptor antagonist-based triplet during carboplatin (AUC ≥4) chemotherapy appears inadequate. A comparative study between olanzapine and NK1 receptor antagonist-based combination is lacking.
20. Distinct CD8+ T cell dynamics associate with response to neoadjuvant cancer immunotherapies.
作者: Housaiyin Li.;Dan P Zandberg.;Aditi Kulkarni.;Simion I Chiosea.;Patricia M Santos.;Brian R Isett.;Marion Joy.;Gabriel L Sica.;Kevin J Contrera.;Curtis M Tatsuoka.;Matthias Brand.;Umamaheswar Duvvuri.;Seungwon Kim.;Mark Kubik.;Shaum Sridharan.;Fei Tu.;Jie Chen.;Tullia C Bruno.;Dario A A Vignali.;Anthony R Cillo.;Riyue Bao.;Jing Hong Wang.;Lazar Vujanovic.;Robert L Ferris.
来源: Cancer Cell. 2025年43卷4期757-775.e8页
We leverage a clinical trial (NCT04080804) that compared neoadjuvant anti-PD-1, anti-PD-1+CTLA-4, and anti-PD-1+LAG-3 therapies in head and neck squamous cell carcinoma patients. Combination therapies promote higher pathologic response rates versus monotherapy, and major pathologic response is associated with better survival. To address whether successful immune checkpoint inhibitor (ICI) regimens act through similar or distinct pathways, we robustly and longitudinally characterize transcriptional and proteomic dynamics of CD8+ tumor-infiltrating lymphocytes (TILs) in a clonal manner. Anti-PD-1+LAG-3 reprograms CD8+ TIL with type-I interferon response and exhaustion gene programs into effector memory and resident memory (TEM/TRM). In contrast, anti-PD-1+CTLA-4 activates and expands pre-existing TEM/TRM CD8+ TIL, but does not rejuvenate exhausted phenotypes into T effector cells. Anti-PD-1+LAG-3, but not anti-PD-1+CTLA-4, induces widespread TCR sharing among the different transcriptional states, as well as increased TCR diversity in responding patients. Our data suggest doublet regimen-specific transcriptional and clonal dynamics of tumor-reactive CD8+ T cells.
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