Mismatch Repair Protein Deficiency Is a Risk Factor for Aberrant Expression of HLA Class I Molecules: A Putative "Adaptive Immune Escape" Phenomenon.
Accumulating evidence indicates that immune checkpoint inhibition-mediated cancer immunotherapies greatly improve the prognosis of certain types of cancer. This approach is now becoming a standard therapy, joining surgery, radiotherapy, and chemotherapy. Because the costs of antibody drugs are now a socioeconomic burden in many countries, an urgent need in cancer immunotherapy is the identification of relevant biomarkers that can predict therapy efficacy. Recent studies have reported that colorectal adenocarcinoma with hereditary or sporadic deficiency in mismatch repair (MMR) proteins has high antigenicity and that detection of these proteins could be a promising way to estimate clinical response. In this study of 135 patients with colorectal cancer, we used immunohistochemistry to investigate the correlation between deficiency in MMR proteins and expression of human leukocyte antigen (HLA) class I molecules, a prerequisite of cytotoxic T-cell-based immunotherapy. Interestingly, MMR protein deficiency was an independent risk factor for the impaired expression of HLA class I molecules (odds ratio (OR)=10.44, 95% confidence interval (CI)=3.15-34.62, p<0.001), suggesting the existence of a putative entity that we have named "adaptive immune escape". Moreover, our results might provide a potential novel biomarker for the selection of patients who would respond to cancer immunotherapies. At the same time, the results suggest that we have to overcome the impaired expression of HLA class I molecules to further improve the cure rate of cancer immunotherapies.
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan kuboteru@sapmed.ac.jp hirohash@sapmed.ac.jp.
Terufumi
T
Kubo
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan kuboteru@sapmed.ac.jp hirohash@sapmed.ac.jp.
Yoshihiko
Y
Hirohashi
Sapporo Clinical Laboratory Inc., Sapporo, Japan.
Kazuhiko
K
Matsuo
Department of Public Health, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tomoko
T
Sonoda
Sapporo Clinical Laboratory Inc., Sapporo, Japan.
Hiroki
H
Sakamoto
Sapporo Clinical Laboratory Inc., Sapporo, Japan.
Kiyoshi
K
Furumura
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tomohide
T
Tsukahara
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Takayuki
T
Kanaseki
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Munehide
M
Nakatsugawa
Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Hiroshi
H
Hirano
Department of Surgical Oncology and Science, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tomohisa
T
Furuhata
Department of Surgical Oncology and Science, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Ichiro
I
Takemasa
Department of Surgical Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tadashi
T
Hasegawa
Department of Pathology, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Toshihiko
T
Torigoe
D000230:Adenocarcinoma / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D053843:DNA Mismatch Repair; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D007223:Infant; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D019139:Tumor Escape; D055815:Young Adult
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I
Adenocarcinoma of the colon; HLA class I molecules; cancer immunotherapy; immune escape; mismatch repair proteins