Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling.
Tumor-infiltrating lymphocytes (TILs) in triple-negative breast cancer (TNBC) have a strong prognostic and predictive significance. However, the mechanism of TIL influx in TNBC is unclear. Expression of major histocompatibility complex class I (MHC I) on the tumor cell is essential for the effective killing of tumor by cytotoxic TILs. In our current study, human leukocyte antigen (HLA) expression was inversely correlated with estrogen receptor (ER) expression in normal and cancerous breast tissue and positively correlated with TILs in breast cancer. The ER score was inversely correlated with TILs in breast cancer. HLA-A and CD8B gene expression was negatively correlated with ESR1 and positively correlated with interferon-associated gene expression in The Cancer Genome Atlas (TCGA) data. Negative correlation between ESR1 and HLA and positive correlation between interferon-associated and HLA gene expression were also confirmed in Cancer Cell Line Encyclopedia (CCLE) data. Taken together, our data suggest that a lower expression of HLA in luminal-type tumors might be associated with low level of TILs in those tumors. Further investigation of the mechanism of higher HLA expression and TIL influx in TNBC may help to boost the host immune response.
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Hee Jin
HJ
Lee
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
In Hye
IH
Song
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
In Ah
IA
Park
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Sun-Hee
SH
Heo
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Young-Ae
YA
Kim
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Jin-Hee
JH
Ahn
Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Gyungyub
G
Gong
D001940:Breast / Q000473:pathology; D016827:CD8 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism*; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism*; D015236:HLA-C Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000378:metabolism; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology
D016827:CD8 Antigens; D047628:Estrogen Receptor alpha; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D007372:Interferons; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C477867:CD8beta antigen; C506487:ESR1 protein, human; C508053:ERBB2 protein, human
Pathology Section; breast carcinoma; human leukocyte antigen; major histocompatibility complex I; tumor-infiltrating lymphocytes