{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:08:46Z","timestamp":1790165326900,"version":"4.1.0"},"reference-count":34,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014418","name":"Harbin Medical University Cancer Hospital","doi-asserted-by":"publisher","award":["N10 project"],"award-info":[{"award-number":["N10 project"]}],"id":[{"id":"10.13039\/100014418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["The major project. No. 81730074"],"award-info":[{"award-number":["The major project. No. 81730074"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,9,9]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Gastric diffuse large B-cell lymphoma (gDLBCL) related to\n                      <jats:italic>Helicobacter pylori<\/jats:italic>\n                      infection exhibits a wide spectrum of prognosis, and the tumor immune microenvironment (TIME) affects tumor progression. However, there are few studies on the correlation between prognosis and changes of TIME induced by\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection in de novo gDLBCL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A retrospective study was performed to determine the prognostic value of TIME related to\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection in de novo gDLBCL. A total of 252 patients were included and have been treated with standard rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy or other similar regimens in addition to\n                      <jats:italic>H. pylori<\/jats:italic>\n                      eradication (HPE). All patients were stratified by\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection, HPE efficacy, and preliminary TIME evaluation using conventional criteria. Statistical analyses were conducted. To assess the mechanism, 30 subjects were assessed for\n                      <jats:italic>H. pylori<\/jats:italic>\n                      infection. The components and spatial distributions of TIME were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median follow-up of the 252 patients was 66.6 months (range 0.7\u2013119.2), and the 5-year overall survival (OS) was 78.0%. A total of 109\n                      <jats:italic>H<\/jats:italic>\n                      .\n                      <jats:italic>pylori-<\/jats:italic>\n                      positive cases with pathological complete remission and high tumor-infiltrating T lymphocytes (cohort 1) had significantly higher 5-year progression-free survival (88.1% vs 70.5%, p&lt;0.001) and OS (89.2% vs 76.6%, p&lt;0.001) than the other 143 patients (cohort 2). Among 30 patients, 19 were cytotoxin-associated gene A-marked as the cohort 1 subset. Compared with cohort 2, cohort 1 exhibited increased inflammatory factors (tumor necrosis factor-\u03b1, interferon \u03b3, etc) and decreased immunosuppressive components (PD-L1, PD-1, IL-10, etc). There was reduced NF-kB activation. Cancer-promoting immune cells (PD-1hiTim-3+ CTL, Tregs, M2-like macrophages, etc) occupied a minor spatial distribution, while the antitumor subtypes increased, corresponding to favorable survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>H. pylori-<\/jats:italic>\n                      evoked inflammatory responses disturb the TIME, causing a differential prognosis in de novo gDLBCL, which can be used to identify patients who could benefit from HPE and immunochemotherapy.\n                    <\/jats:p>\n                  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