Abstract
As around 25-30% of classical Hodgkin Lymphoma (cHL) patients with advanced stages do not respond to standard therapies, the tumor microenvironment (TME) of cHL is one avenue that may be explored with the aim of improving risk stratification. CD4+ T cells are thought to be one of the main cell types in the TME. However, few immune signatures have been studied, and many of these lack related spatial data. Thus, our aim is to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. This study was conducted using the Nanostring GeoMx DSP technology, based on the selection of distinct functional areas of patients' tissues followed by the gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and to seek correlations with clinical metadata. Our results depict a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations, the flux of cytokines and chemokines that could be related to these, and the specific relationships with the clinical outcome.
Overview
- The study aims to spatially resolve the CD4+ T cell subtypes that influence cHL outcome, depicting new immune signatures or transcriptional patterns that are in crosstalk with the tumor cells. The study was conducted using the Nanostring GeoMx DSP technology, based on the selection of distinct functional areas of patients' tissues followed by the gene-expression profiling. The goals were to assess the differences in CD4+ T cell populations between tumor-rich and immune-predominant areas defined by different CD30 and PD-L1 expression levels and to seek correlations with clinical metadata. The study's primary objective is to identify the spatial distribution of CD4+ T cells and their functions in cHL, which could inform the development of new immunotherapies or risk stratification strategies.
Comparative Analysis & Findings
- The study identified a complex map of CD4+ T cells with different functions and differentiation states that are enriched at distinct locations. The flux of cytokines and chemokines that could be related to these was also depicted. The study found that CD4+ T cells with higher expression of CD30 and lower expression of PD-L1 were enriched in tumor-rich areas, while CD4+ T cells with higher expression of CD30 and higher expression of PD-L1 were enriched in immune-predominant areas. The study also found that CD4+ T cells with higher expression of CD30 and lower expression of PD-L1 were associated with a worse clinical outcome. The study's findings suggest that the spatial distribution of CD4+ T cells and their functions could be used to inform the development of new immunotherapies or risk stratification strategies.
Implications and Future Directions
- The study's findings highlight the importance of the spatial distribution of CD4+ T cells and their functions in cHL, which could inform the development of new immunotherapies or risk stratification strategies. The study's limitations include the small sample size and the need for further validation of the findings. Future research directions could include the study of other immune cell types and the exploration of the spatial distribution of these cells in cHL. The study's findings could also be used to inform the development of personalized immunotherapies for cHL patients.