{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T02:54:37Z","timestamp":1772247277711,"version":"3.50.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"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                    Globally, with improvements in general hygiene, the incidence of early childhood (0-4Y-olds\/&amp;lt;5Y-olds) brain and central nervous system (BCNS) cancers is increasing. Although immunological underpinning is suspected, the identification of protective variables for the majority of BCNS cancer cases remains elusive. Extant hypotheses suggest a role for progressively diminishing exposure to common microbes\/pathogens in the rise of childhood cancers in industrialized countries with improved hygiene. Natural exposure to common microbes\/pathogens and childhood vaccinations help train the developing immune system of children to respond appropriately to future infections and maintain a healthy immune system. Considering the established role of childhood vaccinations in augmenting immunity, including \u201ctrained immunity,\" their protective role in pediatric cancers may be surmised. However, a lack of definitive theoretical and practical frameworks to explain conflicting observations has impaired progress. When we analyze the epidemiological data of European region countries with different childhood vaccination policies but more similar socioeconomic conditions, access to medical services, and genetic makeup as compared to other parts of the world, the coverage of seven major childhood (0-1Y-olds) vaccines does not significantly associate with BCNS cancer incidences in the same cohort of 0-4Y-olds (2020). However, interestingly, prevailing tuberculin immunoreactivity, a surrogate for the existence of heterologous cell-mediated immunity resulting from exposure to\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    spp., including Bacille Calmette-Gu\u00e9rin (BCG) vaccination, for these populations, is found consistently negatively correlated with the BCNS cancer incidence in 0-4Y-olds for countries mandating neonatal BCG vaccination [r(24): -0.7226, p-value:&amp;lt;0.0001]. Seemingly, neonatal immune-system priming by BCG and boosting by exposure to environmental\n                    <jats:italic>Mycobacterium<\/jats:italic>\n                    spp. appear protective in 0-4Y-olds. Exploration of BCNS cancer incidence and prevailing immune correlates in matched cohorts, along with prospective randomized controlled trials, may be warranted to conclusively ascertain the impact of childhood vaccinations and boosters (including natural exposure) on early childhood BCNS cancer incidence.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1497436","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T02:16:03Z","timestamp":1737684963000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mycobacterium spp. exposure, childhood vaccinations, and early childhood brain and CNS cancers"],"prefix":"10.3389","volume":"16","author":[{"given":"Samer","family":"Singh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rakesh K.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/s41577-020-00479-7","article-title":"guide to vaccinology: from basic principles to new developments","volume":"21","author":"Pollard","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.chom.2018.12.006","article-title":"Innate and adaptive immune memory: an evolutionary continuum in the host\u2019s response to pathogens","volume":"25","author":"Netea","year":"2019","journal-title":"Cell Host Microbe"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra020100","article-title":"The effect of infections on susceptibility to autoimmune and allergic diseases","volume":"347","author":"Bach","year":"2002","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(99)90437-3","article-title":"Role of microbial burden in aetiology of allergy and asthma","volume":"354","author":"Martinez","year":"1999","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1258\/jrsm.96.8.389","article-title":"Vaccination strategies to reduce the risk of leukaemia and melanoma","volume":"96","author":"Grange","year":"2003","journal-title":"J R Soc Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)48896-4","article-title":"Observations on cancer","author":"De Morgan","year":"1874","journal-title":"Lancet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.610843","article-title":"Vaccination and the risk of childhood cancer-A systematic review and meta-analysis","volume":"10","author":"Marron","year":"2021","journal-title":"Front Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.637087","article-title":"The hygiene hypothesis and new perspectives\u2014Current challenges meeting an old postulate","volume":"12","author":"Garn","year":"2021","journal-title":"Front Immunol"},{"key":"B10","unstructured":"Cancer TODAY\n          \n          \n          CEDEX, France\n          (Data version: Globocan 2022 (version 1.1). 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