Tumor cell PD-L1 predicts poor local control for rectal cancer patients following neoadjuvant radiotherapy

Shao, Lingdong; Peng, Qingqin; Du, Kaifan; He, Jinlan; Dong, Yi; Lin, Xiaojuan; Li, Jinluan; Wang, Junxin

doi:10.2147/cmar.s139889

Cited by 15 publications

(16 citation statements)

References 25 publications

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“…Our study showed the expression difference of LAG-3 and CD8 between the LCRT and SCRT, suggesting that some ICBs and TILs might be modified by the treatment regimens. In accordance with these results, PD-L1 expression in TCs was mostly positive in the SCRT subgroup in our previous study [22]. mmation might be induced by the radiotherapeutic dose and fractionation, also the chemotherapy alongside the LCRT was a consideration.…”

Section: Discussionsupporting

confidence: 89%

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Peng

Xin

et al. 2021

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Many studies have verified the safety of combined radiotherapy and immune checkpoint blockades iation 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 longcourse RT (22.5% vs. 8.0%, P = 0.0440 in ICs; 0% vs. 70%, P < 0.001 in TCs). On the co ntrary, CD8 was higher after long-course RT (15% vs. 8%, P = 0.0146). Interestingly, the level of ICs TIM-3 was low in > 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%

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Section: Discussionsupporting

confidence: 89%

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Peng

Xin

et al. 2021

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“…We found no effect of short-course versus long-course RT on PD-L1+ cells. Shao et al reported, in a retrospective study of 68 rectal cancer patients treated with neoadjuvant RT, that tumor cells PD-L1+ was significantly correlated to short-course RT, suggesting that PD-L1 expression might be regulated by modifying the RT scheme [ 35 ]. This would allow the addition of an immune checkpoint inhibitor targeting PD-1/PD-L1 axis in the adjuvant setting.…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Boustani

Dérangère

Bertaut

et al. 2020

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In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

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“…Based on the inclusion criteria, 15 articles were finally eligible for the meta-analysis. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] A total of 3078 patients from China, South Korea, USA, Japan, Switzerland, and Germany were enrolled. Sample sizes of the studies ranged from 60 to 456 cases.…”

Section: Search Resultsmentioning

confidence: 99%

“…3 Where PD-L1 is expressed may produce different findings. Although previous studies have confirmed that high expression of PD-L1 on TCs was linked with worse survival in CRC patients, 22,31 only a few studies have examined the association between PD-L1 expression on TIICs and prognosis in CRC patients. Recently, two studies revealed that high PD-L1 expression on TIICs was associated with a favorable prognosis in CRC patients.…”

Section: Discussionmentioning

confidence: 99%

Programmed death-ligand 1 and survival in colorectal cancers: A meta-analysis

et al. 2019

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Background: Programmed death-ligand 1 (PD-L1) is a programmed death 1 (PD-1) ligand that plays a pivotal role in the inhibition of the T-cell-mediated immune response. The expression of PD-L1 is associated with the prognosis and clinical outcomes of multiple tumors. However, the prognostic value of PD-L1 overexpression in colorectal cancer is still controversial. In this study, we sought to clarify this by presenting a meta-analysis of relevant studies. Methods: Databases including PubMed, Web of Science, and EMBASE were systematically searched for studies concerning the expression of PD-L1 and survival in colorectal cancer. The reported hazard ratios (HR) with 95% confidence intervals (CI) of overall survival, disease-free survival, and recurrence-free survival in the included studies were analyzed by fixed effects/random effects models. Results: Fifteen studies involving 3078 patients with colorectal cancer were included in our meta-analysis. Overexpression of PD-L1 was found to be associated with poor overall survival (HR 1.83; 95% CI 1.21, 2.79; P = 0.005) and poor recurrence-free survival (HR 2.78; 95% CI 1.43, 5.42; P = 0.003). However, no correlation was found between PD-L1 overexpression and poor disease-free survival (HR 1.23; 95% CI 0.83, 1.82; P = 0.305). Overexpression of PD-L1 indicating poor survival held true across different geographical areas, sample sizes, analysis types, sources of HRs, and cell types. Conclusion: Overexpression of PD-L1 is associated with worse prognosis in patients with colorectal cancer and can guide physicians in the application of PD-1/PD-L1 immune checkpoint-targeted therapy.

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Tumor cell PD-L1 predicts poor local control for rectal cancer patients following neoadjuvant radiotherapy

Cited by 15 publications

References 25 publications

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Assessment of the expression and response of PD-1, LAG-3, and TIM-3 after neoadjuvant radiotherapy in rectal cancer

Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Programmed death-ligand 1 and survival in colorectal cancers: A meta-analysis

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