Abstract 1240P
Background
Immune checkpoint inhibitors are used as the standard treatments for advanced esophageal squamous cell carcinoma (ESCC). Although programmed cell death-ligand 1 (PD-L1) expression is associated with clinical outcome, the clinical utility of PD-L1 expression is still limited. Recent studies have identified the balance of programmed cell death 1 (PD-1) expression between CD8+T cells and regulatory T (Treg) cells in the tumor microenvironment as a biomarker for ICIs.
Methods
We retrospectively reviewed ESCC patients who received nivolumab for whom formalin-fixed paraffin-embedded specimens obtained prior to nivolumab were available. Multiple immunostaining analysis was performed to examine the relationship between PD-1+CD8+T cells and PD-1+Treg cells expression rates and their antitumor effects, which were compared between responders (complete response, partial response, or stable disease ≥6 months) and non-responders (stable disease <6 months or progressive disease). This study population was divided into high and low expression groups, and progression-free survival (PFS) was compared between these two groups.
Results
Matched tissue results were available in 87 patients. The overall analysis showed that the expression rate of PD-1+ CD8+T cells in tumors was not significantly different between responders and non-responders (66.3% vs 57.1%, p=0.46), but the expression rate of PD-1+ Treg cells tended to be higher in non-responders than in responders (15.4 cells/mm2 vs 4.4 cells/mm2, p=0.057). In addition, the PD-1 positivity rate of Treg cells to CD8+ T cells was significantly higher in non-responders than in responders (0.69 vs 0.17, p=0.037). PFS was significantly longer in the low expression group with a PD-1 positivity rate of Tregs to CD8+ T cells below the median of 0.56 than in the high expression group (median PFS: 3.3 months vs 1.8 months; hazard ratio [95%CI]: 0.56 [0.34-0.92], p=0.02).
Conclusions
The expression rate of PD-1+Treg cells in the tumor environment and the balance of PD-1 expression between CD8+T cells and Treg cells is a new promising biomarker for predicting the efficacy of nivolumab in advanced ESCC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Yamamoto: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol-Myers Squibb. Y. Honma: Financial Interests, Personal, Advisory Board: Janssen, Eisai; Financial Interests, Personal and Institutional, Invited Speaker: Taiho Pharmaceutical, Chugai Pharma, MSD, Novartis, GlaxoSmithKline, Jannsen. T. Kashihara: Financial Interests, Personal, Invited Speaker: AstraZeneca. H. Igaki: Financial Interests, Personal, Advisory Role: HekaBio; Financial Interests, Personal, Invited Speaker: Varian Medical Systems, Itochu, Himedic; Financial Interests, Personal, Research Grant: Elekta, CICS, HekaBio. S. Koyama: Financial Interests, Personal, Invited Speaker: Chugai Pharmacetical; Financial Interests, Personal, Advisory Role: Kaken Pharmaceutical; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Bristol-Myers Squibb, Otsuka Pharmaceutical. H. Nishikawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bristol-Myers Squibb, Chugai Pharma, Eisai; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Bristol-Myers Squibbmaceutical, Chugai Pharma, Eisai, Daiichi Sankyo, Astellas Pharma, Becton Dickinson, SRL Diagnostics, Fujifilm, Bayer Yakuhin, Rakuten Medical, Hitachi, Janssen Research & Development, Merck Sharp & Dohme, Taiho Pharmaceutical, Kyowa Kirin, Zenyaku Kogyo, Oncolys BioPharma, Debiopharm Group, Asahi Kasei, Sysmex, Sumitomo Dainippon Pharma. K. Kato: Financial Interests, Personal, Invited Speaker: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical, Bristol Myers Squibb, Merck and Co, Bayer, AstraZeneca, Beigene, Taiho, Merck Biophrma, Amgen, Novartis; Financial Interests, Personal, Expert Testimony: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: ONO Pharmaceuticals, Merck & Co, Bayer, AstraZeneca, Beigene, Chugai, Taiho, Oncolys Biopharma, Janssen Pharmaceutical. All other authors have declared no conflicts of interest.