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K. Kurose
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-018 - Correlation of Clinical Response and XAGE1 Immunity in Lung Adenocarcinoma (ID 8446)
09:30 - 09:30 | Author(s): K. Kurose
- Abstract
Background:
Cancer/testis (CT) antigen is a class of antigens that express predominantly in the testes and various tumor types. Some CT antigens have been shown to be highly immunogenic and are considered to be attractive targets for cancer immunotherapy. We identified XAGE1 as a dominant CT antigen in lung adenocarcinoma (LAD). In this study, we investigated the correlation of clinical response and XAGE1 immunity in LAD.
Method:
XAGE1 antigen expression and immune checkpoint molecules were determined with tumor tissues by immunohistochemistry. The XAGE1 antibody and T-cell immune responses, as well as immune cell phenotypes, were analyzed with blood samples. The overall survival (OS) of the XAGE1 antigen-positive and -negative, and XAGE1antibody-positive and -negative patients were investigated.
Result:
The XAGE1 antigen is expressed in 30 to 40% of LAD. In pStage I-IIIA LAD, expression of the XAGE1 antigen was correlated with shortened OS in both Hokkaido (n=77) and Kawasaki (n=120) cohort, suggesting its relation to malignancy. Based on the expression profiles of XAGE1, and immune checkpoint molecules of PD-L1 and Galectin-9 on tumor cells, we developed a discriminant function capable of efficiently predicting OS in pStage I-IIIA LAD. The XAGE1 antibody response was observed 6% (9/155) in pStage I-IIIA, and 20% (34/167) in cStage IIIB-IV LAD, respectively, suggesting a higher antibody response rate in more advanced stage patients. In the antibody-positive patients, CD4 and CD8 T-cell responses were frequently elicited, and phenotypic and functional analyses of T cells indicated immune activation. Furthermore, we revealed that the OS of antibody-positive patients was prolonged significantly compared with that of antibody-negative patients with either XAGE1 antigen-positive EGFRwt (31.5 vs. 15.6 months, P = 0.05) or EGFRmt (34.7 vs. 11.1 months, P = 0.001) LAD. Multivariate analysis showed that XAGE1 antigen expression was a worse predictor in patients with EGFRmt tumors (HR: 5.23). On the other hand, the presence of the XAGE1 antibody was a strong predictor for prolonged OS in patients with XAGE1 antigen positive tumors (HR: 0.18) and in patients with either EGFRwt or EGFRmt tumors.
Conclusion:
Frequent antibody and T cell responses indicate the strong immunogenicity of the XAGE1 antigen. The findings suggest that production of XAGE1 antibody predicts good prognosis of lung adenocarcinoma patients as an immune biomarker and sheds light on the role of the protective effect of this naturally occurring immune response supporting the concept of immunotherapy.
