{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T03:29:23Z","timestamp":1786418963985,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The efficacy of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains heterogeneous. The real\u2010world efficacy and comparison of triplet regimens against doublet regimens is unclear. Moreover, the immunological mechanisms underlying differential responses to NAC are poorly understood. This study aimed to compare the efficacy of doublet versus triplet NAC in a Chinese LAGC cohort, and characterize the post\u2010treatment tumor immune microenvironment (TIME) to identify immune correlates of response and survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study enrolled patients with locally advanced gastric cancer (GC) who received NAC followed by D2 gastrectomy. The clinical outcomes of patients treated with different NAC regimens were analyzed. The TIME was further characterized using fluorescent multiplex immunohistochemistry (mIHC) to analyze the density and spatial proximity of the immune cells the SOX regimen group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 141 GC patients with complete survival data were included in the final analysis. The overall efficacy of NAC was consistent with prior reports: 7.8% (11\/141) achieved ypT0, 36.2% (51\/141) achieved ypN0, and 6.4% (9\/141) attained a pathological complete response (pCR). Triplet regimens did not provide a statistically significant survival and response advantage over doublet regimens. mIHC analysis showed longer DFS were consistently associated with higher densities of effector immune cells and lower densities of exhausted\/immunosuppressive subsets. Favorable survival was also linked to a closer spatial proximity of CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells to tumor cells. In treatment response subgroups, responders exhibited distinct spatial patterns, including higher overall CD56\n                      <jats:sup>+<\/jats:sup>\n                      cell density but fewer CD68\n                      <jats:sup>+<\/jats:sup>\n                      cells near tumors, alongside a shorter CD56\n                      <jats:sup>+<\/jats:sup>\n                      \u2010to\u2010tumor distance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study confirms the consistent anticancer efficacy of neoadjuvant chemotherapy in LAGC. To better inform individualized post\u2010NAC treatment strategies, analysis of the TIME using multiplex mIHC on surgical specimens is recommended.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72132","type":"journal-article","created":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:31:49Z","timestamp":1784953909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluorescent Multiplex Immunohistochemistry (\n                    <scp>mIHC<\/scp>\n                    ) Analyses of Local Advanced Gastric Cancer Patients After Neoadjuvant Chemotherapy Revealed the Status of Tumor\u2010Infiltrating Immune Cells and Predicted the Clinical Outcome"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9622-1198","authenticated-orcid":false,"given":"Miaomiao","family":"Gou","sequence":"first","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhe","family":"Gao","sequence":"additional","affiliation":[{"name":"The First Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7375-7296","authenticated-orcid":false,"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niansong","family":"Qian","sequence":"additional","affiliation":[{"name":"The Eighth Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haixu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanju","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7025-735X","authenticated-orcid":false,"given":"Zhikuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Qiao","sequence":"additional","affiliation":[{"name":"The First Medical Center of Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7339-3840","authenticated-orcid":false,"given":"Guanghai","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology Chinese PLA General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"issue":"3","key":"e_1_2_10_3_1","first-page":"221","article-title":"Cancer Incidence and Mortality in China, 2022","volume":"46","author":"Zheng R. 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