Erschienen in:
03.01.2020 | Original Article
Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer
verfasst von:
In Hye Song, Young-Ae Kim, Hyeonjin Lee, Hye Seon Park, In Ah Park, Chan Kyu Sim, Myeong Sup Lee, Gyungyub Gong, Hee Jin Lee
Erschienen in:
Immunologic Research
|
Ausgabe 6/2019
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Abstract
The expression of major histocompatibility complex class I (MHC I) in tumor cells is regulated by interferon signaling, and it is an important factor in the efficacy of cytotoxic T cell–dependent immunotherapy. To determine the impact of immune cells in MHC I expression on tumor cells, we compared the expression of MHC I in tumor cells derived from primary breast cancers and patient-derived xenograft (PDX) models. MHC I and myxovirus resistance gene A (MxA) expression were analyzed using immunohistochemistry in 23 cases of tumor tissue and corresponding primary and secondary PDXs. The median H score of MHC I was 210 (0–300) in patient tumor tissues, 197.5 (0–300) in primary PDX tumors, and 157.5 (5–300) in secondary PDX tumors. Cases were divided into four groups based on the difference in MHC I expression between the patient tumor tissues and secondary PDXs. Eleven cases constituted the high MHC I group, four constituted the low MHC I group, six comprised the decreased MHC I group, and two comprised the increased MHC I group. MHC I and MxA expressions in each tumor were weakly correlated within patients’ tumors, while strongly correlated within PDX models. Retained or altered expression of MHC I in breast cancer PDXs reveals the presence of intrinsic and extrinsic interferon signaling pathways in tumor cells. Thus, considering MHC I expression in PDX is important when using PDX models to evaluate the efficacy of cancer immunotherapy in a preclinical setting.