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

Abstract

Purpose To 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. Methods Three 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. Results PD-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. Conclusion Overall, 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.

Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment

“…Our findings are in line with mounting evidence supporting a relationship between PD‐L1 expression in immune cells and more favourable clinical outcomes 17,18 …”

Circulating Protein Biomarkers for Prognostic Use in Patients with Advanced Pancreatic Ductal Adenocarcinoma Undergoing Chemotherapy

“…The second overlapping protein between the two indices, PDCD1, also known as programmed cell-death protein 1 (PD-1), has been widely studied, and the axis of PD-1 and its ligand, PD-L1, are considered the most successful target for immune checkpointblockade therapy to date [31]. PD-L1 has been shown to be a prognostic marker in several cancer types [32][33][34].…”

Tumor budding in gastric adenocarcinoma; reflections on tumor microenvironment and programmed death ligand 1 (PD-L1) expression

“…In the context of the tumor microenvironment, a low tumor budding /high TILs status could be a potential candidate for anti-PD-L1 treatment. While the relationship between tumor budding and PD-L1 expression is still not clear, Lang-Schwarz et al (4) reported an inverse relationship between tumor budding and PD-L1 expression in colorectal cancer. Furthermore, they found that a low tumor budding/high TILs status showed higher PD-L1 expression levels than other combinations.…”

“…Tumor stroma percentage (TSP) and immune response factors, such as tumor-infiltrating DOI:10.34172/ipp.2022.31365 lymphocytes (TILs), are identified as signs of tumor progression. The interactions among these factors contributed to the development of immunotherapy through the identification of multiple immune checkpoints (4).…”

“…TILs have recently gained research attention in many cancers, including GAC, as a prognostic feature and indicator for immunotherapy. High TILs are generally associated with good prognosis (3,4).…”