Abstract

Objectives:Detection of Immunohistochemical (IHC) expression of PDL-1 by tumor cells and stromal tumor infiltrating lymphocytes (TILs) in colorectal carcinoma, to investigate the possibility of using it as a targeted therapy, as well as, correlation of this expression with the clinico-pathologic parameters of the tumors. Materials and Methods:Colorectal tissue sections were collected from 60 colectomy specimens were taken from Kasr El Ainy Hospital, Faculty of Medicine, Cairo University. Exclusion criteria included cases with missing data and cases who received chemotherapy or radiotherapy. IHC expression of PDL-1 was investigated in tumor cells (T) and stromal TILs separately. PDL-1 positivity was defined as PDL-1 expression on ≥ 5% of membranous positive cell staining of any intensity. Results:PDL-1 (T) expression was detected in 25% of cases and showed statistically significant correlation with higher tumor grade and right sided colon tumors (P value < 0.05). PD-L1 stromal TILs expression was detected in 38.3 % of cases. Insignificant statistical relation between Stromal TILs PDL-1 expression and the tumor extent (T) was detected (P value = 0.07), however, the expression of PDL-1 in lymphocytes was inversely proportional to the tumor extent (invasion). There were linear relation between PDL-1 expression stromal (TILs) (33.3%) and PDL-1 expression in tumor cells (28.2%) and positive lympho-vascular invasion but it was statistically insignificant (P value = 0.4 and 0.2 respectively). Despite there were no statistical relation between either PDL-1 (T) and PDL-stromal TILS and Perineural invasion (P value =1 and 0.5) but inverse relation was noticed with more PDL-1 expression in tumor cells (24.5%) and TILS (40.8%) with negative Perineural invasion. Conclusion:Our results supported PDL-1 expression in CRC by both TC and TILs, with higher expression in subset of tumors that are high grade highlighting them as candidates for anti- PD-1/PDL-1 therapy.

Highlights

  • CRC is the third most common cancer worldwide after lung and breast cancers with two-thirds of all CRCs occurring in the more developed regions of the world (Gado et al, 2013)

  • Despite there were no statistical relation between either PDL-1 (T) and PDL-stromal TILS and Perineural invasion (P value =1 and 0.5) but inverse relation was noticed with more PDL-1 expression in tumor cells (24.5%) and TILS (40.8%) with negative Perineural invasion

  • Despite there were no statistical relation between both PDL-1 (T) and stromal TILS with Perineural invasion (P value= 1 and 0.5) but inverse relation was noticed with more PDL-1 expression in tumor cells and TILS with negative Perineural invasion

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Summary

Introduction

CRC is the third most common cancer worldwide after lung and breast cancers with two-thirds of all CRCs occurring in the more developed regions of the world (Gado et al, 2013). The development of CRC is a complex and heterogeneous process arising from an interaction between multiple etiological factors, including genetic factors and environmental factors, such as diet and lifestyle (Ioannou et al, 2015). The immune system recognizes cancer cells as soon as they emerge. The interaction between T cells and antigen-presenting cells (APC) is complex and involves the T cell receptor and multiple co-regulatory receptors, which exert both activating and inhibitory stimuli to the T cell (Muenst et al, 2014). Despite the large number of tumor antigens induced by genetic and epigenetic changes found in all cancers, tumors resist immune attack by inducing tolerance among tumor-specific T cells and by expressing ligands that engage inhibitory receptors and

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