Programmed death ligand 1 (PD-L1) in colon cancer and its interaction with budding and tumor-infiltrating lymphocytes (TILs) as tumor-host antagonists

Corinna Lang-Schwarz,William Sterlacci,Michael Vieth,Arndt Hartmann,Simone Bertz,Balint Melcher,Theresa Dregelies,Klaus Lang-Schwarz

doi:10.1007/s00384-021-03985-9

Abstract

PurposeTo analyze the role of programmed death ligand 1 (PD-L1) immunohistochemisty in the context of tumor microenvironment in colon cancer (CC) with focus on the interaction between tumor budding and tumor-infiltrating lymphocytes (TILs) and to elucidate its potential value for immunooncologic treatment decisions.MethodsThree hundred forty seven patients with CC, stages I to IV, were enrolled. PD-L1 immunohistochemistry was performed using two different antibodies (clone 22C3 pharmDx, Agilent and clone QR1, Quartett). Tumor proportion score (TPS) as well as immune cell score (IC) was assessed. Budding and TILs were assessed according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) and International TILs Working Group (ITWG). Correlation analyses as well as survival analyses were performed.ResultsPD-L1 positivity significantly correlated with TILs > 5% and MMR deficiency, and PD-L1-positive cases (overall and IC) showed significantly longer overall survival (OS) with both antibodies.The parameters “high grade,” “right-sidedness,” and “TILS > 5% regardless of MMR status” evolved as potential parameters for additional immunological treatment decisions. Additionally, TPS positivity correlated with low budding. More PD-L1-positive cases were seen in both high TIL groups. The low budding/high TIL group showed longer disease-free survival and longer OS in PD-L1-positive cases.ConclusionOverall, PD-L1 positivity correlated with markers of good prognosis. PD-L1 immunohistochemistry was able to identify parameters as additional potential candidates for immune therapy. Furthermore, it was able to stratify patients within the low budding/high TIL group with significant prognostic impact.

Highlights

IntroductionTreatment regimens were based on the tumor node metastasis (TNM) staging system, the grading according to the World Health Organization (WHO) classification and molecular biomarkers [2]
Colorectal cancer (CRC) is one of the most common cancer types worldwide
Treatment regimens were based on the tumor node metastasis (TNM) staging system, the grading according to the World Health Organization (WHO) classification and molecular biomarkers [2]

Summary

Introduction

Treatment regimens were based on the tumor node metastasis (TNM) staging system, the grading according to the World Health Organization (WHO) classification and molecular biomarkers [2]. The discovery of immune checkpoint inhibitors has revolutionized cancer treatment regimes, and checkpoint inhibitors have already become part of the therapeutic standard in different human cancer types, for example (but not limited to), lung cancer, malignant melanoma, and breast cancer [3,4,5,6]. In mismatch repair-deficient (dMMR) metastatic colon cancer (CC), the progammed death 1 (PD-1) inhibitor pembrolizumab led to a significantly longer progression-free survival than chemotherapy when applied as first-line therapy and showed fewer treatment-related adverse events [7]. In June 2020, the US Food and Drug Administration (FDA) approved pembrolizumab (KEYTRUDA, Merck Sharp Dohme) for the first-line treatment of patients with

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