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J. Persson
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MA 05 - Immuno-Oncology: Novel Biomarker Candidates (ID 658)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Yoichi Nakanishi, P. Mitchell
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 303 + 304
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MA 05.13 - Scavenger Receptor MARCO Defines a Targetable Tumor-Associated Macrophage Subset in Lung Cancer (ID 8641)
15:45 - 17:30 | Author(s): J. Persson
- Abstract
- Presentation
Background:
Tumor-associated macrophages (TAMs) with immunosuppressive and tumor promoting features are attractive targets for immunotherapy. MARCO is a scavenger receptor expressed on a subpopulation of macrophages in secondary lymphoid organs. A recent study performed in animal models concluded that treatment with an anti-MARCO antibody results in reprogramming of the TAMs and inhibition of tumor growth and metastatic spread. The expression and function of MARCO in lung cancer TAMs is not known.
Method:
The infiltration of TAMs expressing MARCO, CD68, CD163 and MSR1, in the tumor and stromal compartments, was analyzed by immunohistochemistry in a non-small cell lung cancer (NSCLC) cohort (n=352). In addition, PD-L1 expression was assessed on tumor cells. Immunofluorescence was performed on selected cases to evaluate marker co-expression. Associations to immune cells and regulatory inflammatory pathways were studied in a subset of cases (n=174) with available RNA-seq data.
Result:
A large variance in TAM density could be observed between cases as well as a strong correlation between CD68 and CD163, indicating a pro-tumor phenotype of infiltrating macrophages. Correlation to clinical data showed a trend towards worse survival for patients with high macrophage infiltration. TAM expression of MARCO was seen on a subpopulation of pro-tumor macrophages. The majority of MARCO expressing TAMs were found to be located within tumor cell nests. Interestingly, stromal macrophages expressing MARCO tended to aggregate in close proximity to the tumor nests. On the transcriptomic level, increased MARCO gene expression correlated to genes linked to immunosuppressive TAMs, T-cell infiltration and immune checkpoint molecules like PD-L1 and CTLA-4. The association between macrophage infiltration and tumor cell PD-L1 expression was confirmed by immunohistochemistry. Also, co-expression of PD-L1 and MARCO could be detected on certain macrophages within the tumor cell nests.
Conclusion:
MARCO expression characterizes a specific subpopulation of pro-tumor macrophages that are enriched in PD-L1 positive NSCLC cases. Patients with significant infiltration of MARCO positive TAMs could benefit from treatment with anti-MARCO antibodies, possibly in combination with available immune checkpoint inhibitors.
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MA 06 - Lung Cancer Biology I (ID 660)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Biology/Pathology
- Presentations: 1
- Moderators:N. Motoi, Keith M Kerr
- Coordinates: 10/16/2017, 15:45 - 17:30, Room 501
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MA 06.01 - Cancer Testis Antigens and Mutational Load in Relation to the Immune Landscape of Non-Small Cell Lung Cancer (ID 9369)
15:45 - 17:30 | Author(s): J. Persson
- Abstract
- Presentation
Background:
The avoidance of immune surveillance by tumor cells is an accepted hallmark of cancer. The aim of this study was to describe the natural immune landscape of NSCLC tissue, to identify important regulatory associations and potential targets of immune response. This includes mutational load and cancer testis antigen (CTA) expression, and the comprehensive analysis of tumor infiltrating immune cells in connection with immune signaling and clinical information.
Method:
Tissue microarrays including duplicate cancer samples of 357 NSCLC patients were stained with antibodies against CD3, CD4, CD8, CD45RO, FoxP3, CD20, CD138, and CD44 to analyze the protein expression in the stroma and tumor compartment. For 197 of these cases, corresponding RNA-seq data were available. The immunological data were correlated to the transcriptomic data and to patients’ clinical outcome. The mutation status and the mutational load was based on a targeted next-generation sequencing panel of 82 genes (HaloPlex).
Result:
The immune cell infiltration was predominantly in the stroma, although CD8 and FoxP3 cells also showed relevant infiltration of the tumor cell compartment. The amount of T-cells of different subsets and CD20-positive B-cells correlated positively to each other. A higher mutational load was associated with higher CD8 T-cell infiltrates, CD45RO cells, FoxP3 regulatory cells as well as CD20-positive B-cells in the tumor compartment. In contrast, the number of expressed CTAs were associated with an abundance of CD45RO-positive cells in the stromal compartment. Only CD44-positivity (HR = 0.61, p< 0.01) as well as high CD20 positive B-cells (HR = 0.34, p< 0.01) and plasma cell (CD138, HR = 0.71, p< 0.05) counts in the tumor, and for plasma cells also the stromal (HR = 0.61, p< 0.01), compartment were associated with longer overall survival.
Conclusion:
Here we describe natural immune profiles in a large clinical NSCLC patient cohort. Interestingly both mutational load and CTA expression is associated with the abundance of distinct immune cell infiltrates. We could not confirm the impact of tumor infiltrating T-cells on survival. However, the consistent prognostic impact of both B-cell markers indicates a major role of the humoral immune response in lung cancer.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
