Home FOR AUTHORS Neoplasma Ahead of print neo_2021_201210N1341

Journal info


6 times a year.
Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

Editorial Info
Abstracted and Indexed
Submission Guidelines

Select Journal







Webshop Cart

Your Cart is currently empty.

Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

neo_2021_201210N1341

Title: Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer
Author: Qing-Qin Peng, Jin-Luan Li, Pei-Ling Xin, Kai-Xin Du, Xiao-Yi Lin, Jun-Xin Wu, Mu-Tian Zhang, Xiang-Quan Kong

Abstract:

Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades (ICBs) without the specific radiation dose or sequencing of combination. We aimed to evaluate the expression and response of PD-1, TIM-3, LAG-3 after neoadjuvant radiotherapy (NRT) and explore the possibility and optimal schedule of combining immunotherapy with radiotherapy in treating rectal cancer. Immunohistochemistry was performed to detect the expression of PD-1, TIM-3, LAG-3, CD8, and CD3. These molecules' expression was detected on the specimens of 76 rectal cancer patients following NRT and 13 of these patients before NRT.
The expression of ICBs was assessed by the percentage of positive cells. The levels of PD-1 and immune cells (ICs) LAG-3 in rectal cancer increased after NRT (0% vs. 3%, P = 0.043 and 5% vs. 45%, P = 0.039, respectively). However, TIM-3 in ICs and tumor cells (TCs) were both decreased (80% vs. 50%, P = 0.011, 90% vs. 0%, P = 0.000, respectively). The LAG-3 expression was higher in patients treated with short-course RT than long-course RT (22.5% vs. 8.0%, P = 0.0440 in ICs; 0% vs. 70%, P eight weeks after long-course RT (P = 0.045). The expressions of PD-1, ICs TIM-3, ICs LAG-3, CD3, and CD8 were associated with the disease-free survival (DFS) in univariate analysis (P = 0.036, 0.008, 0.018, 0.025, and 0.004, respectively). Adjusted by the relevant variables, PD-1 (HR 0.274; 95% CI 0.089-0.840; P = 0.024) and ICs TIM-3 (HR 0.425; 95% CI 0.203-0.890; P = 0.023) were independent prognostic factors of DFS in rectal cancer patients following NRT. In conclusion, we have identified that PD-1 and ICs LAG-3 presented a trend towards increased expression after NRT, supporting the ICBs and NRT combination as a potential treatment option for local advanced rectal cancer patients. The radiotherapeutic mode and timing of the treatment might significantly affect the expression of ICBs, which indicated that the sequencing and time window of ICBs immunotherapy utility might deserve a high value.



Keywords: PD-1; TIM-3; LAG-3; rectal cancer; radiotherapy
Published online: 13-Apr-2021
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2021_201210N1341


download file



© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.