{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T18:05:31Z","timestamp":1779473131538,"version":"3.53.1"},"posted":{"date-parts":[[2025,10,6]]},"group-title":"Cancer Biology","reference-count":10,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RP200315"],"award-info":[{"award-number":["RP200315"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["CA296049"],"award-info":[{"award-number":["CA296049"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Preclinical cancer models often use subcutaneous (SC) implantation, which fails to recapitulate the native tumor microenvironment (TME) of orthotopic (ORT) sites. To resolve these differences, we used single-cell RNA sequencing (scRNA-seq) on paired SC and ORT implants of the CKP syngeneic gastric cancer model. Histopathological differences were minimal, but scRNA-seq revealed profound TME divergence. ORT tumors displayed robust stromal activation, coordinated fibroblast and endothelial signaling, and an immune compartment marked by higher T\/NK cell activation and IgA-biased B cell plasma programs, reflecting a physiological mucosal environment. In contrast, SC tumors had higher overall T cell infiltration but showed markedly increased CD8+ T cell exhaustion and an enriched oxidative tumor program. Our findings provide critical guidance: SC models are optimal for high-throughput and exhaustion-focused assays, whereas ORT models are indispensable for studying organ-specific immune and stromal biology with translational fidelity.<\/jats:p>","DOI":"10.1101\/2025.10.03.680400","type":"posted-content","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:55:18Z","timestamp":1759776918000},"source":"Crossref","is-referenced-by-count":1,"title":["Comparative single-cell transcriptomics of orthotopic and subcutaneous gastric tumors reveal immune and stromal heterogeneity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2668-241X","authenticated-orcid":false,"given":"Jinho","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7243-5386","authenticated-orcid":false,"given":"Yoojeong","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-5972","authenticated-orcid":false,"given":"Kyung-Pil","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sohee","family":"Jun","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0737-2654","authenticated-orcid":false,"given":"Jae-Il","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Experimental Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"},{"name":"Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052210250648000_2025.10.03.680400v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0495-5"},{"key":"2026052210250648000_2025.10.03.680400v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00709-3"},{"key":"2026052210250648000_2025.10.03.680400v2.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2024.108631"},{"key":"2026052210250648000_2025.10.03.680400v2.4","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0044"},{"issue":"5","key":"2026052210250648000_2025.10.03.680400v2.5","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1158\/2767-9764.CRC-25-0008","article-title":"Impact of Subcutaneous Versus Orthotopic Implantations on Patient-Derived Xenograft Transcriptomic Profiles","volume":"5","year":"2025","journal-title":"Cancer Res Commun"},{"issue":"8","key":"2026052210250648000_2025.10.03.680400v2.6","first-page":"458","article-title":"Single-cell transcriptomic sequencing identifies subcutaneous patient-derived xenograft recapitulated medulloblastoma","volume":"8","year":"2025","journal-title":"Animal Model Exp Med"},{"key":"2026052210250648000_2025.10.03.680400v2.7","doi-asserted-by":"crossref","unstructured":"Seo Y , Jang J , Ko KP , Zou G , Huang Y , Zhang S , Zhang J , Jun S , Chu W , Venkatesan V , Dhakshinamoorthy S , Park JI . 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