Comparative analysis of the immune microenvironment in histological subtypes of lung and breast cancer using a tissue microarray (TMA) comprising invasive margin (IM) and tumour centre (TC)

Abstract

Abstract Background Immunotherapy is proving successful in several tumour settings, although many cancer types remain less responsive. Pre-existing tumour infiltrating lymphocytes and PD-L1 expression associate with response to immunotherapy and cancers have been classified into response subtypes according to these biomarkers. To enable a simultaneous comparative assessment of the immune microenvironment in multiple tumour indications, we have constructed a multi-tumour TMA comprising matched cores for each donor from IM and TC. Methods In this study, we employed a TMA comprising cores taken from formalin fixed paraffin embedded (FFPE) non-treated surgical resections for donors diagnosed with squamous NSCLC (SCC; n = 13), adeno NSCLC (ADC; n = 12), small cell lung cancer (SCLC; n = 9), oestrogen receptor positive breast cancer (ER+BC; n = 12), Herceptin positive BC (Her2+BC; n = 12) and triple negative BC (TNBC; n = 12). Serial sections were stained by immunohistochemistry for several immune biomarkers (CD163, CD68, PD-L1, CD8, CD3, PD-1, Foxp3, CD4, CD20). Immune infiltrates were analysed by digital image analysis and PD-L1 was scored by a pathologist to deliver both the tumour proportion score (TPS) and the combined positivity score (CPS). Results By taking an average of all cores (IM and TC) for each disease indication, we demonstrate that SCC, ADC and TNBC are more highly infiltrated, and that while tumour PD-L1 (TPS) was absent in ER+BC and Her2+BC, the contribution from infiltrating immune cells (CPS) was greatest in SCC and TNBC. Interestingly, a reciprocal profile for CD163:CD68 was observed for LC versus BC, with the M2-like CD163+ macrophage/monocytic population exceeding the CD68+ macrophage population in BC, whereas the converse was observed for LC. Immune infiltrates were reduced in TC compared with IM, and distinct case-by-case immune microenvironments were revealed within each disease indication. Conclusion Using an immuno-oncology focussed TMA we have revealed distinct immune profiles in multiple tumour subtypes simultaneously, providing a valuable basis against which to profile novel immune targets. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure M. Bhagat: Shareholder / Stockholder / Stock options, Officer / Board of Directors: TriStar Technolgoy Group. All other authors have declared no conflicts of interest.