Abstract 1990P
Background
Complete and durable responses are seen in only a fraction of cancer patients receiving immunotherapy and a significant proportion of patients fail to respond. While high levels of tumour infiltrating T cells are believed to correlate with response to immunotherapy in many solid cancers, the presence of high levels of macrophages are associated with worse prognosis.
Methods
To investigate the relationship of T cells to macrophages across multiple cancer types simultaneously, we constructed a set of 5 tissue microarray (TMA) slides each comprising 144 cores (1mm). In total, 28 different tumour indications were included, with an average of 12 cases per tumour type, each case represented by duplicate cores (1 from invasive margin [IM]; 1 from tumour centre [TC]). Serial sections were stained for CD3 (2GV6) and CD68 (PG-M1) by single-plex immunohistochemistry, and immune cells enumerated by digital image analysis (CellProfilerTM).
Results
In the first instance, T cell and macrophage infiltration for each tumour indication was examined by taking the average of all cores regardless of location (IM or TC) for each marker. As expected, some tumour types such as HRPC, renal and GBM exhibited low T cell counts whereas other tumours were highly infiltrated (e.g. NSCLC, gastric). Interestingly, a higher CD68:CD3 ratio was observed for lower T cell infiltrated tumours (e.g. HRPC 2.4; GBM 3.1; renal 2.8; ovarian 2.5), whereas the converse was evident for more highly infiltrated tumours (e.g. NSCLC ADC 1.3; gastric 0.6, cutaneous SCC 0.5). Furthermore, comparison of IM versus TC revealed an immune excluded phenotype exemplified by low T cells in the TC, for some tumour indications (e.g. ovarian, cervical); an observation that was associated frequently with higher CD68:CD3 ratio in the IM.
Conclusions
Although these data demonstrate considerable heterogeneity between cases with respect to immune phenotypes, examination of multiple tumour indications concurrently have highlighted disease settings where macrophages predominate over T cells potentially shaping an immunosuppressive microenvironment that may limit the immunostimulatory activity of tumour infiltrating T cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
TriStar Technology Group, LLC.
Funding
TriStar Technology Group, LLC.
Disclosure
M. Bhagat: Shareholder/Stockholder/Stock options, Officer/Board of Directors, President & CEO: TriStar Technolgoy Group. All other authors have declared no conflicts of interest.