{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:44:58Z","timestamp":1782895498996,"version":"3.54.5"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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. Immunol."],"abstract":"<jats:p>\n                    Tuberculosis (TB), caused by\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb), remains the leading cause of death from a single infectious agent worldwide, with 10.7 million new cases and 1.23 million deaths reported globally in 2024. Although conventional chemotherapy cures most drug-susceptible TB, the rising burden of multidrug-resistant TB (MDR-TB), prolonged treatment regimens, and suboptimal patient adherence continue to undermine control efforts. Against this background, immunotherapeutic approaches have gained renewed interest as rational complements to chemotherapy, building on decades of mechanistic work that has mapped host\u2013pathogen interactions at unprecedented resolution. This review integrates recent advances across the immunotherapy landscape, including next-generation vaccines (M72\/AS01E, MTBVAC, VPM1002, BNT164 mRNA candidates), host-directed therapies (HDTs) targeting autophagy, metabolic and inflammatory pathways, cytokine-based and antimicrobial peptide strategies, and adoptive cell therapies. We place particular emphasis on the dual, context-dependent roles of immune checkpoints such as PD-1\/PD-L1 in TB, where checkpoint blockade can paradoxically trigger reactivation, and on the cellular heterogeneity revealed by single-cell and spatial transcriptomics of the granuloma. Key translational challenges\u2014the absence of reliable correlates of protection, the demand for precision immunomodulation in comorbid populations (HIV, diabetes), and chronic underfunding of TB research\u2014are discussed alongside emerging opportunities offered by mRNA platforms, repurposed drugs, and multi-omics\u2013guided patient stratification. Collectively, immunotherapy is evolving from an adjunctive concept into a strategic pillar of TB control, with the potential to shorten treatment, prevent relapse, and address drug-resistant disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1859046","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T07:56:07Z","timestamp":1782892567000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunotherapy for tuberculosis: current landscape, mechanistic insights, and translational perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Yanlang","family":"He","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, Shaoyang Central Hospital","place":["Shaoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangping","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Shaoyang Central Hospital","place":["Shaoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangyan","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Shaoyang Central Hospital","place":["Shaoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Medicine, The Second Affiliated Hospital of Wannan Medical College","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Changsha Medical University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of General Medicine, The Second Affiliated Hospital of Wannan Medical College","place":["Wuhu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","volume-title":"Global Tuberculosis Report 2025","year":"2025"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60844-8","article-title":"Global, regional, and national incidence, prevalence, and mortality of HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013","volume":"384","author":"Murray","year":"2014","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD016013.pub2","article-title":"Diabetes as a risk factor for tuberculosis disease","volume":"8","author":"Franco","year":"2024","journal-title":"Cochrane Database Syst Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy675","article-title":"Undernutrition and tuberculosis: public health implications","volume":"219","author":"Sinha","year":"2019","journal-title":"J Infect Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10071157","article-title":"Past, present and future of Bacillus Calmette-Gu\u00e9rin vaccine use in China","volume":"10","author":"Li","year":"2022","journal-title":"Vaccines (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00109904","article-title":"The dream of a vaccine against tuberculosis; 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