title: The extent of inflammatory infiltration in primary cancer tissues is associated with lymphomagenesis in immunodeficient mice.
abstract: Xenotransplantation of human cancers into immunodeficient mice is a very useful approach for studying human tumor biology. However, the occasional occurrence of lymphomagenesis in some mice can spoil the model and must be investigated in detail. We found that a high percentage (32.5%, 26/80) of cancer patient-derived xenografts (PDXs) resembled lymphoma in NOD/SCID mice. Of the 26 xenografts, 23 were human-derived expressing human CD45 (hCD45+) and proved to be of the B-cell subtype (CD3-/CD20+), and they were all positive for Epstein-Barr virus (EBV). The remaining 3 xenografts proved to be mouse-derived for both hCD45- and negative amplification of a human gene. The most interesting finding is that gastric cancer had much higher rates (24/126, 19.0%) of lymphoma formation in the PDX model than did colorectal cancer (1/43, 2.3%). Statistical analysis revealed that cancer type and inflammation in the parent tumor are significantly associated with lymphomagenesis. Further validation discovered lymphomagenesis by inoculating only gastritis mucosa. Therefore, our findings suggest that it is necessary to take precautions when directly xenografting cancer tissues with remarkable baseline inflammation, such as gastric cancer into immunodeficient NOD/SCID strains. Further, the established xenograft models should be validated by both leukocyte markers and human gene signatures.
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Lianhai
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.affiliation: BeiGene (Beijing) Co. Ltd, No. 30 Science Park Road, Life Science Park, Changping District, Beijing, China.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Shuangxi
authors.initials: S
authors.lastname: Li
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Zong
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhaode
authors.initials: Z
authors.lastname: Bu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Aiwen
authors.initials: A
authors.lastname: Wu
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Xiaozheng
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Kang
authors.affiliation: BeiGene (Beijing) Co. Ltd, No. 30 Science Park Road, Life Science Park, Changping District, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: BeiGene (Beijing) Co. Ltd, No. 30 Science Park Road, Life Science Park, Changping District, Beijing, China.
authors.forename: David
authors.initials: D
authors.lastname: Sutton
authors.affiliation: BeiGene (Beijing) Co. Ltd, No. 30 Science Park Road, Life Science Park, Changping District, Beijing, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wang
authors.affiliation: BeiGene (Beijing) Co. Ltd, No. 30 Science Park Road, Life Science Park, Changping District, Beijing, China.
authors.forename: Lusong
authors.initials: L
authors.lastname: Luo
authors.affiliation: Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Surgery, Peking University Cancer Hospital and Institute, Beijing, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D063646:Carcinogenesis / Q000276:immunology*; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000821:virology; D017493:Leukocyte Common Antigens; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD / Q000821:virology; D016513:Mice, SCID / Q000821:virology; D014183:Transplantation, Heterologous / Q000379:methods*
chemical_list: D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
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