Abstract 1244P
Background
Myeloid cells are the majority of cellular components in the immune system. We previously identified myeloid subsets expressing immune checkpoint molecules, including CTLA4, PD1, and LAG3, as key effector cells that promote tumor progression and metastasis, and lead to treatment resistance in mice and human. However, the prognostic impact of these subsets remains to be determined, particularly in advanced gastric cancer (AGC) patients receiving nivolumab monotherapy (NIVO) that provides limited efficacy.
Methods
We conducted flow cytometric analysis of tumor-infiltrating cells (TILs) and peripheral blood cells (PBCs) obtained from 91 AGC patients before and after NIVO between August 2018 and November 2020. Progression-free survival (PFS) and overall survival (OS) were compared between high/low groups divided by the cutoff value determined by visually assessing the continuous trend and change point of log hazard ratios obtained by applying penalized splines to each biomarker. This study was supported by ONO PHARMACEUTICAL CO., LTD. and Bristol Myers Squibb, and approved by IRB at each participating institution.
Results
In the TIL analysis using samples before NIVO, high group showed shorter PFS/OS compared with low group divided by CD11b+CTLA4+ (median [m] PFS 27 vs 67 days, HR = 2.37, p = 0.001/ mOS 103 vs 228 days, HR = 2.02, p = 0.013), and CD11b+LAG3+ (mPFS 35 vs 60 days, HR = 2.23, p = 0.003/ mOS 104 vs 228 days, HR = 1.71, p = 0.070), showing relatively stronger association compared to CD11b+PD1+ (mPFS 43 vs 60.5 days, HR = 1.58, p = 0.043/ mOS 140 vs 222.5 days, HR = 1.48, p = 0.122) and CD11b+PDL1+ (mPFS 42 vs 60 days, HR = 1.77, p = 0.024/ mOS 105 vs 219 days, HR = 1.75, p = 0.040). In the PBC analysis using samples before NIVO, high group showed shorter PFS/OS compared with low group divided by CD11b+CTLA4+ (mPFS 49.5 vs 99 days, HR = 1.76, p = 0.029/ mOS 167 vs 393 days, HR = 1.63, p = 0.101), and CD11b+LAG3+ (mPFS 46 vs 60.5 days, HR = 1.70, p = 0.017/ OS median 178 vs 185 days, HR = 1.19, p = 0.483).
Conclusions
High proportions of CTLA4+ and LAG3+ myeloid subsets in TIL and PBC before treatment were associated with poor prognosis after NIVO in AGC patients, suggesting that these molecules can be a strong target of the new treatment strategy for AGC.
Clinical trial identification
UMIN000032686.
Editorial acknowledgement
Legal entity responsible for the study
Narikazu Boku.
Funding
ONO PHARMACEUTICAL, Brstol-Myers Squibb.
Disclosure
N. Boku: Financial Interests, Institutional, Research Grant: ONO PHARMACEUTICAL, Takada Pharmaceutical; Financial Interests, Personal, Invited Speaker: ONO PHARMACEUTICAL, Bristol-Myers Squibb, Taiho Pharmaceutical, Daiichi-Sankyo. N. Takahashi: Financial Interests, Personal, Invited Speaker: ONO PHARMACEUTICAL, Bristol-Myers Squibb, Taiho Pharmaceutical. T. Kawakami: Financial Interests, Personal, Invited Speaker: ONO PHA, Bristol-Myers Squibb. N. Okano: Financial Interests, Personal, Invited Speaker: ONO PHARMACEUTICAL, Taiho pharmaceutical, Eli Lilly, Eizai, Bayer, Chugai, Takeda pharmaceucital, GlaxoSmithKline. Y. Narita: Financial Interests, Personal, Invited Speaker: ONO PHARMACEUTICAL, Bristol-Myers Squibb, Eli Lilly, Taiho pharmaceutical, Daiichi Sankyo. Y. Yamamoto: Financial Interests, Personal, Invited Speaker: Takeda pharmacetical, Chugau, Taiho Pharmaceutical, Sanofi, Yakult, Nihon Servier, Eli Lilly, Asahi Kasei Parma, ONO PHARMACEUTICAL. K. Nagashima: Financial Interests, Personal, Invited Speaker: Phizer, Fujimoto Pharmaceutical, SENJU Pharmaceutical, Toray Industries. K. Aoki: Financial Interests, Personal, Invited Speaker: ONO PHARMACEUTICAL, Chugai, Eisai, Daiichi Sankyo, Chiome Bioscience. K. Muro: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, ONO PHARMACEUTICAL, Chugai, Eli Lilly, Daiichi Snakyo, Taiho pharmaceutical, Brstol-Myers Squibb. All other authors have declared no conflicts of interest.