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S.D. Martin



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    MA 10 - Immunotherapy I (ID 664)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      MA 10.09 - Increased T Follicular Helper Cell Infiltration in Lung Adenocarcinoma Tertiary Lymphoid Organs (ID 8487)

      12:00 - 12:05  |  Author(s): S.D. Martin

      • Abstract
      • Presentation
      • Slides

      Background:
      T follicular helper cells (Tfh) are an antigen-experienced CD4+ T cell subset that have been found to play crucial roles in the development of humoral immunity. In particular, their presence in the B cell-rich germinal centre of secondary and tertiary lymphoid tissue aids in B cell maturation through selection of B cells producing high-affinity antibodies. Tfh cells have known roles in autoimmune disease and B cell malignancies; however, their role in many solid tumours, including those of the lung, remains unclear.

      Method:
      We analyzed 83 paired tumour-normal lung adenocarcinoma samples from the BC Cancer Agency (BCCA) as well as 576 unpaired samples from The Cancer Genome Atlas (TCGA). Relative immune cell content was obtained from gene expression data using a linear support vector regression deconvolution approach (CIBERSORT). Spatial positioning of B and T cells within selected tumour sections was examined through IHC. The impact of Tfh infiltration on patient survival was analyzed using a Cox Proportional Hazard model.

      Result:
      T follicular helper cells are increased in tumour tissue, accompanied by global upregulation of Tfh markers PDL1 and CXCR5 in both the BCCA and TCGA cohorts. Histological analysis revealed localization of Tfh cells within tertiary lymphoid organs, with direct contact with B cells in the follicular zone observed. Importantly, Tfh recruitment appears to be an early event in tumour development and a function of neoantigen exposure, indicative of an active anti-tumour response rather than a result of chronic inflammation of the tumour microenvironment.

      Conclusion:
      T follicular helper cells are required for B cell maturation and subsequent antibody responses. As such, it is not surprising that Tfh infiltration in tumour-resident ectopic lymphoid structures correlates with patient survival in various cancer types. Given the importance of tumour-specific antibody responses in natural and therapeutic immunity, further investigation of Tfhs may show prognostic utility and be a marker of early-stage lung tumours.​

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