Severely immunocompromised NOD.Cg- Prkdc scid Il2rg tm1Sug (NOG) mice are among the ideal animal recipients for generation of human cancer models. Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes (TILs) can induce xenogeneic graft- versus- host disease (xGvHD) following engraftment and expansion of the TILs inside the animal body. Wilms' tumor (WT) has not been recognized as a lymphocyte- predominant tumor. However, 3 consecutive generations of NOG mice bearing WT patient- derived xenografts (PDX) xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention. In the initial generation, dermatitis, auto- amputation of digits, weight loss, lymphadenopathy, hepatitis, and interstitial pneumonitis were observed. Despite antibiotic treatment, no response was noticed, and thus the ani-mals were prematurely euthanized (day 47 posttransplantation). Laboratory and his-topathologic evaluations revealed lymphoid infiltrates positively immunostained with anti- human CD3 and CD8 antibodies in the xenografts and primary tumor, whereas no microbial infection or lymphoproliferative disorder was found. Mice of the next generation that lived longer (91 days) developed sclerotic skin changes and more severe pneumonitis. Cutaneous symptoms were milder in the last generation. The xenografts of the last 2 generations also contained TILs, and lacked lymphoprolifera-tive transformation. The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD. While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts, this report for the first time documented serial xGvHD in consecutive passages of WT PDX- bearing models and discussed potential solutions to prevent such an undesired complication.

Seyed Mostafa Monzavi;Ahad Muhammadnejad;Maryam Behfar;Amir Arsalan Khorsand;Samad Muhammadnejad;Abdol-Mohammad Kajbafzadeh

Department of Applied Cell Sciences,School of Advanced Technologies in Medicine,Tehran University of Medical Sciences,Tehran,Iran;Pediatric Urology and Regenerative Medicine Research Center,Tehran University of Medical Sciences,Tehran,Iran;Gene Therapy Research Center,Digestive Diseases Research Institute,Tehran University of Medical Sciences,Tehran,Iran;Cancer Biology Research Center,Cancer Institute of Iran,Tehran University of Medical Sciences,Tehran,Iran;PDX Platform,Biomarker Evaluation and Supervision Team for Personalized Medicine,Molecular Tumor Board,Cancer Institute of Iran,Tehran University of Medical Sciences,Tehran,Iran;Pediatric Cell and Gene Therapy Research Center,Tehran University of Medical Sciences,Tehran,Iran

动物模型与实验医学（英文）

[1]Seyed Mostafa Monzavi;Ahad Muhammadnejad;Maryam Behfar;Amir Arsalan Khorsand;Samad Muhammadnejad;Abdol-Mohammad Kajbafzadeh-.Spontaneous xenogeneic GvHD in Wilms ' tumor Patient- Derived xenograft models and potential solutions)[J].动物模型与实验医学（英文）,2022(04):389-396

Prkdc,scid,Il2rg,tm1Sug,nfiltrating,xGvHD,xenotransplanted,topathologic,immunostained,sclerotic,lymphoprolifera,immunoinflammatory,lymphodominant

Spontaneous,xenogeneic,Wilms,Patient,Derived,models,potential,solutions,Severely,immunocompromised,NOD,Cg,NOG,mice,are,among,ideal,animal,recipients,human,cancer,Transplantation,solid,tumors,having,abundant,lymphocytes,TILs,induce,versus,host,disease,following,engraftment,expansion,inside,body,WT,has,been,recognized,predominant,However,consecutive,generations,bearing,patient,derived,xenografts,PDX,from,single,donor,showed,different,degrees,symptoms,after,before,any,therapeutic,intervention,In,initial,dermatitis,auto,amputation,digits,weight,loss,lymphadenopathy,hepatitis,interstitial,pneumonitis,were,observed,Despite,antibiotic,treatment,response,was,noticed,thus,mals,prematurely,euthanized,posttransplantation,Laboratory,evaluations,revealed,lymphoid,infiltrates,positively,CD3,CD8,antibodies,primary,whereas,microbial,infection,lymphoproliferative,disorder,found,Mice,next,that,lived,longer,days,developed,skin,changes,more,Cutaneous,milder,last,also,contained,lacked,transformation,systemic,syndrome,absence,suggestive,While,there,few,reports,severely,immunodeficient,this,first,documented,serial,passages,discussed,prevent,such,undesired,complication

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