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Erin L Schenk
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P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P14.20 - Multi-Spectral Imaging of Lung Adenocarcinoma Reveals Importance of Cancer Specific HLA-DR on the TME and Clinical Outcome (ID 3666)
00:00 - 00:00 | Presenting Author(s): Erin L Schenk
- Abstract
Introduction
Within the tumor microenvironment (TME), the interactions between cancer cells and immune cells are of increasing importance as targeting key immune checkpoints have redefined clinical care for patients with lung cancer. While immune checkpoint inhibitors have improved outcomes for patients with NSCLC, only a subset of patients respond. Tremendous efforts have been made to define factors that mediate tumor progression and response to immunotherapy. Regulation of antigen-presentation has been shown to play a critical role in this response. MHCII (HLA-DR) is normally expressed on antigen presenting cells and leads to activation of CD4+ T cells. Notably, HLA-DR expression is observed on cancer cells and appears to shape local anti-tumor immunity through potential direct presentation of tumor neoantigens to CD4+ helper T cells. While several studies have demonstrated that HLA-DR on cancer cells leads to more T cell infiltration, its effect on the TME and outcomes for patients with NSCLC have not been systemically examined. Advances in multispectral immunohistochemistry techniques allow for quantitative and spatial identification of multiple immune cells. Imaging with multiple markers can reveal the diversity of the local immune infiltrate, cell-cell interactions, and correlations of spatial distribution and location of immune cells in NSCLC with clinical outcome of patients with cancer cells.
Methods
Slides from 153 patients with resected lung adenocarcinoma were stained using Opal multiplex with a panel of markers: DAPI, HLA-DR, CK, CD3, CD14, CD19 and CD8. Multispectral imaging was performed using wide field microscopy on the Vectra3.0. For each patient, 3-5 regions of interest (ROIs) were chosen and spectral unmixing was utilized for the detection and separation of seven different fluorescent signals in each NSCLC tissue samples. Cells were segmented based on nuclear and membrane markers and classified in phenotypes using inForm machine learning algorithms. The immunophenotypes were quantified and nearest neighbor analysis was performed. The presence of HLA-DR on cancer cells and immune cell infiltration were correlated with clinical outcome.
Results
Co-expression of HLA-DR and CK+ defined cancer cells that express MHCII. HLA-DR high and HLA-DR low patients were stratified using a cutoff of >5% of cancer cells expressing HLA-DR. Patients with HLA-DR high tumors had significantly increased immune cell infiltration of CD4+, CD8+, and CD14+ cells. Nearest neighbor analysis demonstrated CK+ tumor cells in HLA-DR high patients were in closer proximity to CD14+, CD19+, CD4+, and CD8+ T cells. In HLA-DR high patients, more CK+ cancer cells were directly interfaced with CD4+ and CD8+ T cells. Patients with high levels of cancer cell HLA-DR experienced improved overall survival at 5 years (p=0.046).
Conclusion
HLA-DR high tumors are significantly associated with increased T cell and myeloid cell infiltration, resulting in closer proximity of all immune cells and more cell-cell contact. Imaging analysis of HLA-DR high tumors demonstrated more direct contact with CD4+ and CD8+ T cells compared to HLA-DR low tumors. Patients with HLA-DR high tumors experienced an improved overall survival compared to patients with HLA-DR low tumors. These data suggest cancer cell HLA-DR may represent a new biomarker for TME inflammation and patient outcomes in NSCLC.
