{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:26:02Z","timestamp":1781951162582,"version":"3.54.5"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) are standard care for advanced non-small cell lung cancer (NSCLC), yet patients with active tuberculosis (TB) are consistently excluded from clinical trials. Furthermore, data guiding the use of dual PD-1\/CTLA-4 blockade in the presence of multidrug-resistant TB (MDR-TB) is lacking. We report a 56-year-old man with stage IVA pulmonary squamous cell carcinoma (SqNSCLC) who progressed on multiple lines of therapy, including chemotherapy plus pembrolizumab, docetaxel, and the PD-1\/VEGF bispecific antibody ivonescimab. During treatment, he developed secondary MDR-TB. Following stabilization with a WHO-recommended all-oral MDR-TB regimen and palliative radiotherapy for a progressive metastatic lesion, he was rechallenged with QL1706 (a unified PD-1\/CTLA-4 bispecific antibody). The patient achieved sustained stable disease with a progression-free survival (PFS) of approximately 11 months. Crucially, strict multidisciplinary monitoring confirmed no TB reactivation or dissemination, and no grade \u22653 immune-related adverse events occurred. This case provides the first clinical evidence that, in carefully selected patients with controlled MDR-TB, dual checkpoint blockade with QL1706 is a feasible salvage strategy, provided that TB is rigorously managed.<\/jats:p>","DOI":"10.3389\/fonc.2026.1775568","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:55Z","timestamp":1776313255000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: PD-1\/CTLA-4 dual checkpoint blockade(QL1706) in advanced pulmonary squamous cell carcinoma complicated by multidrug-resistant tuberculosis after multiple lines of immunotherapy"],"prefix":"10.3389","volume":"16","author":[{"given":"Li","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Oncology, Guiyang Public Health Clinical Center","place":["Guiyang, China"]},{"name":"Department of Oncology, Guiyang Cancer Hospital","place":["Guiyang, China"]},{"name":"Department of Oncology, Guiyang Fifth People\u2019s Hospital, Guiyang","place":["Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, Guiyang Public Health Clinical Center","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aat2702","article-title":"Tuberculosis following PD-1 blockade for cancer immunotherapy","volume":"11","author":"Barber","year":"2019","journal-title":"Sci Transl Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2102512","DOI":"10.1183\/13993003.02512-2021","article-title":"The paradox of immune checkpoint inhibition re-activating tuberculosis","volume":"60","author":"Ahmed","year":"2022","journal-title":"Eur Respir J"},{"key":"B4","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s13045-023-01445-1","article-title":"First-in-human phase I\/Ib study of QL1706, a bifunctional PD-1\/CTLA-4 dual blocker, in patients with advanced solid tumors","volume":"16","author":"Zhao","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41392-024-01741-x","article-title":"QL1706 plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort phase II study","volume":"9","author":"Huang","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-025-02160-6","article-title":"Iparomlimab and tuvonralimab: first approval","volume":"85","author":"Keam","year":"2025","journal-title":"Drugs"},{"key":"B7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13045-025-01728-9","article-title":"Iparomlimab and tuvonralimab plus chemotherapy and bevacizumab for EGFR-mutant NSCLC after EGFR-TKIs: results from DUBHE-L-201 cohort 5","volume":"18","author":"Zhang","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B8","volume-title":"WHO consolidated guidelines on tuberculosis. Module 4: Treatment \u2013 drug-resistant tuberculosis","year":"2022"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1016\/j.cell.2017.07.024","article-title":"Distinct cellular mechanisms underlying anti-CTLA-4 and anti-PD-1 checkpoint blockade","volume":"170","author":"Wei","year":"2017","journal-title":"Cell"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.03.015","article-title":"Immune checkpoint inhibitor use and tuberculosis: a systematic review of the literature","volume":"132","author":"Zaemes","year":"2020","journal-title":"Eur J Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002960","article-title":"Risk of tuberculosis in patients with cancer treated with immune checkpoint inhibitors: a nationwide observational study","volume":"9","author":"Bae","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1162190","article-title":"Tuberculosis infection following immune checkpoint inhibitor treatment for advanced cancer: a case report and literature review","volume":"14","author":"Lin","year":"2023","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.12.003","article-title":"Infectious complications associated with the use of immune checkpoint inhibitors: reactivation of tuberculosis after anti-PD-1 treatment","volume":"24","author":"Picchi","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx225","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Haanen","year":"2017","journal-title":"Ann Oncol"}],"updated-by":[{"DOI":"10.3389\/fonc.2026.1896026","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000}}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1775568\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T09:30:12Z","timestamp":1781170212000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1775568\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":14,"alternative-id":["10.3389\/fonc.2026.1775568"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1775568","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"article-number":"1775568"}}