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Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer

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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.

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Funding

This work was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI15C0708 and HI17C0337); Basic Science Research Programs through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (NRF-2016R1D1A1B03935367 and NRF-2018R1D1A1B07040612); and the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (2016-169).

Author information

Correspondence to Gyungyub Gong or Hee Jin Lee.

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Conflict of interest

The authors declare that that they have no conflict of interest.

Ethical approval

This study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Asan Medical Center (IRB#2015-0438) and the International Animal Care and Use Committee (IACUC) of the Laboratory of Animal Research at the Asan Medical Center, Seoul, Republic of Korea.

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Informed consent was obtained from all individual participants included in the study.

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Précis

Tumor cells derived from PDX models showed retainment or alteration of MHC I expression. Thus, considering MHC I expression in PDX is important when using PDX models to evaluate the efficacy of cancer immunotherapy in a preclinical setting.

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Song, I.H., Kim, Y., Lee, H. et al. Retained or altered expression of major histocompatibility complex class I in patient-derived xenograft models in breast cancer. Immunol Res 67, 469–477 (2019). https://doi.org/10.1007/s12026-019-09109-4

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Keywords

  • Breast carcinoma
  • Tumor-infiltrating lymphocytes
  • Major histocompatibility complex I
  • Human leukocyte antigen