Development of a microbead based immunoassay to detect circulating soluble HLA-E: Application in cancer immunobiology

• Published in: Journal of clinical oncology Vol. 41; no. 16_suppl; p. e17606
• Main Authors: Kanangat, Varun, Auger, Claire, Tarhoni, Imad, Marshalla, Megan K., Gerard, David, Abdelkader, Ahmed
• Format: Journal Article
• Language: English
• Published: American Society of Clinical Oncology 01.06.2023
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2023.41.16_suppl.e17606

e17606Background: The Human Leukocyte Antigens [HLA] gene complex is subdivided into classical (HLA-A, B, and C) and non-classical (HLA-E, F, G, and H) loci. These genes are associated with immune modulation and immunopathogenesis in cancer, though the roles of non-classical HLA molecules are poorly understood. Here, we explored potential expression patterns of soluble HLA-E (sHLA-E) in patient sera across a range of common malignancies to identify potential disease applications for future study. Methods: Quantitative Luminex immunobead assay were developed for sHLA-E using methods we previously defined. In the first phase of this study, we assessed sHLA-E protein levels across a range of treatment-naïve metastatic malignancies (n=5 each), including breast, lung adenocarcinoma, lung squamous cell carcinoma, colorectal, head and neck, ovarian, melanoma, and sarcoma. Based on these results, we refocused our efforts on a second cohort surgically treated by gynecologic oncology for either non-malignant (n=13) or malignant (n=42) lesions of ovarian origins. One-way ANOVA or Independent sample t tests, with normality confirmed via Levene's Test for Equality of Variances, were used to identify statistical relationships. Results: There were significantly (p<0.05) higher levels of sHLA-E protein in ovarian cancer relative to other cancer types surveyed. In the second phase of the study, serum specimens from patients undergoing surgery for a suspected gynecological malignancy were tested for sHLA-E. This study also showed the significantly high expression of sHLA-E in ovarian cancer relative to those with nonmalignant lesions of ovarian origins (p=0.035) that was independent of FIGO grade (p>0.05). For comparison, levels of sHLA-E were not significantly elevated for tumors of endometrium/ endomyometrium origins (n=76; p=0.270) relative to baseline of benign cases. Conclusions: We identified a highly specific statistical relationship for a circulating isoform of HLA-E in ovarian cancer in our cohorts. The significance of these findings in relation to clinical outcomes or treatment response will be explored in future studies. Ovarian origin - BenignOvarian origin - CancerNumber1342Median Age (range)67 (41-80)65.5 (40-82)FIGO Grade (range)NA3 (2-4)% Stages III-IVNA82.3%Median [HLA-E] (range)0.92 ng/mL (0.2-14.6)1.42 ng/mL (0.18-1000)p-value (Benign vs. Cancer)NA0.035