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. 2024 Jul 21;16(14):2606.
doi: 10.3390/cancers16142606.

PD-L1 Expression in Paired Samples of Rectal Cancer

Mina Coussement  1 , Roberta Fazio  1 , Alessandro Audisio  1 , Reem El Khoury  1 , Fatima-Zahra Abbassi  1 , Irene Assaf  1 , Chiara Conti  1 , Chiara Gallio  1 , Nada Benhima  1 , Giacomo Bregni  1 , Paraskevas Gkolfakis  1 , Valentina Spagnolo  1 , Geraldine Anthoine  1 , Gabriel Liberale  1 , Luigi Moretti  1 , Philippe Martinive  1 , Alain Hendlisz  1 , Pieter Demetter  2   3 , Francesco Sclafani  1
Affiliations

PD-L1 Expression in Paired Samples of Rectal Cancer

Mina Coussement et al. Cancers (Basel). .

Abstract

Immune checkpoint inhibitors and immune-related biomarkers are increasingly investigated in rectal cancer (RC). We retrospectively analysed PD-L1 expression in diagnostic biopsy and resection samples from RC patients treated at our centre between 2000 and 2020. PD-L1 immunostaining (22C3 clone) was evaluated according to tumour proportion (TPS), immune cell (ICS), and the combined positive score (CPS). Eighty-three patients were included. At diagnosis, PD-L1 expression ≥1%/≥5% was observed in 15.4%/0%, 80.7%/37.4%, and 69.2%/25.6% of patients based on TPS, ICS, and CPS, respectively. At surgery, the respective figures were 4.6%/1.5%, 60.2%/32.5%, and 50.7%/26.2%. Using the 1% cut-off and regardless of the scoring system, PD-L1 was less expressed in surgery than biopsy samples (p ≤ 0.04). In paired specimens, PD-L1-ICS reduction was especially observed following neoadjuvant long-course (chemo)radiotherapy (p = 0.03). PD-L1-ICS of ≥5% in surgical samples (HR: 0.17; p = 0.02), and a biopsy-to-surgery increase in PD-L1-ICS (HR: 0.19; p = 0.04) was predictive for longer disease-free survival, while the PD-L1-ICS of either ≥1% (HR 0.28; p = 0.04) or ≥5% (HR 0.19; p = 0.03) in surgical samples and the biopsy-to-surgery increase in PD-L1-ICS (HR: 0.20; p = 0.04) were associated with better overall survival. Our study suggests that PD-L1 expression in RC is largely reflective of immune cell infiltration, and its presence/increase in surgical samples predicts better outcomes.

Keywords: PD-L1; combined positive score (CPS); immune cell score (ICS); immune checkpoint inhibitors; radiotherapy; rectal cancer; tumour proportion score (TPS).

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Conflict of interest statement

Alain Hendlisz: consultancy, advisory roles, and honoraria from Amgen, Bayer, Eli Lilly, Merck, Pierre Fabre, Servier, and Sirtex. Research funding (institutional) from Amgen, Astra Zeneca, Ipsen, Leo Pharma, Merck, Roche, Sanofi, and Teva Pharma. Support for travel/accommodation from Merck, Roche, and Sirtex. Francesco Sclafani: consultancy, advisory roles, and honoraria: AMAL Therapeutics, Amgen, Bayer, BMS, Dragonfly Therapeutics, GSK, Merck, Nordic Pharma, Roche, and Servier; research funding (institute): Amgen, Astellas, Astra Zeneca, Bayer, BMS, Merck, MSD, Pierre-Fabre, and Roche, Sanofi; travel grants: Amgen, Bayer, Lilly, Merck, Roche, and Servier; and leadership roles: Secretary EORTC Gastrointestinal Tract Cancer Group. All the other authors do not have any conflicts of interest.

Figures

Figure 1
Figure 1
PD-L1 expression ≥1% according to TPS, IC and CPS in biopsy and surgical specimens. * p value < 0.05; ** p value < 0.01. Abbreviations: CPS, combined positive score; ICS, immune-cell score; TPS, tumour proportion score.
Figure 2
Figure 2
Disease-free and overall survival according to PD-L1 by ICS in surgical samples (a,b), and according to change in PD-L1 expression by ICS in paired specimens (c,d). Abbreviations: ICS, immune-cell score; DFS, disease-free survival; OS, overall survival.
See this image and copyright information in PMC

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