Efficacy and safety of immune checkpoint inhibitors in elderly patients with primary liver cancer: a retrospective, multicenter, real-world cohort study

Xiao, Lushan; Liao, Yanxia; Wang, Jiaren; Li, Qimei; Zhu, Hui; Chang, Hong; Li, Ruining; He, Jingzhe; Cui, Hao; Dong, Hanzhi; Zhou, Lin; Liu, Li

doi:10.1007/s00262-023-03417-3

Cited by 3 publications

(4 citation statements)

References 39 publications

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“…PD-1 inhibitors are the T cell-based immune checkpoint blockade, which can recognize the PDCD1 (PD-1, CD279) of CD8+ T cells. The immune response of CD8+ T cells is activated when PDCD1 is blocked ( 29 , 30 ). First, the expression level of PDCD1 was analyzed in immune cells and esophageal tissues.…”

Section: Resultsmentioning

confidence: 99%

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Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells

He,

Yang,

Lin

et al. 2024

Front. Immunol.

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BackgroundEsophageal cancer (ESCA) is one of the most common tumors in the world, and treatment using neoadjuvant therapy (NT) based on radiotherapy and/or chemotherapy has still unsatisfactory results. Neoadjuvant immunochemotherapy (NICT) has also become an effective treatment strategy nowadays. However, its impact on the tumor microenvironment (TME) and regulatory mechanisms on T cells and NK cells needs to be further elucidated.MethodsA total of 279 cases of ESCA who underwent surgery alone [non-neoadjuvant therapy (NONE)], neoadjuvant chemotherapy (NCT), and NICT were collected, and their therapeutic effect and survival period were compared. Further, RNA sequencing combined with biological information was used to analyze the expression of immune-related genes. Immunohistochemistry, immunofluorescence, and quantitative real-time PCR (qRT-PCR) were used to verify the activation and infiltration status of CD8+ T and CD16+ NK cells, as well as the function and regulatory pathway of killing tumor cells.ResultsPatients with ESCA in the NICT group showed better clinical response, median survival, and 2-year survival rates (p < 0.05) compared with the NCT group. Our RNA sequencing data revealed that NICT could promote the expression of immune-related genes. The infiltration and activation of immune cells centered with CD8+ T cells were significantly enhanced. CD8+ T cells activated by PD-1 inhibitors secreted more IFN-γ and cytotoxic effector factor cells through the transcription factor of EOMES and TBX21. At the same time, activated CD8+ T cells mediated the CD16+ NK cell activation and secreted more IFN-γ to kill ESCA cells. In addition, the immunofluorescence co-staining results showed that more CD276+ tumor cells and CD16+ NK cells were existed in pre-NCT and pre-NICT group. However, CD276+ tumor cells were reduced significantly in the post-NICT group, while they still appeared in the post-NCT group, which means that CD16+ NK cells can recognize and kill CD276+ tumor cells after immune checkpoint blocker (ICB) treatment.ConclusionNICT can improve the therapeutic effect and survival period of resectable ESCA patients. NICT could promote the expression of immune-related genes and activate CD8+ T and CD16+ NK cells to secrete more IFN-γ to kill ESCA cells. It provides a theoretical basis and clinical evidence for its potential as an NT strategy in ESCA.

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Section: Resultsmentioning

confidence: 99%

“…However, there is still controversy over the options and models of NT for ESCA. Especially in the era of immunotherapy, many solid tumors have shown significant benefits in treatment with the participation of ICBs ( 30 , 33 ). Similarly, traditional NT for ESCA is also facing challenges from immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells

He,

Yang,

Lin

et al. 2024

Front. Immunol.

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“…Our previous study results suggest that lymph node metastasis and splenomegaly is an independent prognostic factor for PLC in immunotherapy [ 44 – 46 ]. A meta-analysis provided strong or highly suggestive evidence that NLR is associated with cancer prognosis [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study

Sun

Jian

et al. 2023

Discov Onc

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Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan–Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan–Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.

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“…Furthermore, in HCC patients receiving ICIs combined with radiotherapy treatment, older patients aged 65 years or older showed better responses to ICIs in terms of both PFS (HR=0.955, P=0.037) and OS (HR=0.931, P<0.001) (29).In another multicenter retrospective study involving 540 patients treated with ICIs, patients aged 65 years or older responded better to ICIs in terms of DCR and PFS, while maintaining similar ORR and OS (128). The analysis of public datasets revealed that the elderly group had lower expression of oncogenic pathways such as PI3K-Akt, Wnt, and IL-17, and higher tumor mutation burden compared to younger patients (128).…”

Section: Agementioning

confidence: 93%

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

Qin,

Jin,

2023

Front. Immunol.

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In recent years, immune checkpoint inhibitors (ICIs) have emerged as a transformative approach in treating advanced hepatocellular carcinoma (HCC). Despite their success, challenges persist, including concerns about their effectiveness, treatment costs, frequent occurrence of treatment-related adverse events, and tumor hyperprogression. Therefore, it is imperative to identify indicators capable of predicting the efficacy of ICIs treatment, enabling optimal patient selection to maximize clinical benefits while minimizing unnecessary toxic side effects and economic losses. This review paper categorizes prognostic biomarkers of ICIs treatment into the following categories: biochemical and cytological indicators, tumor-related markers, imaging and personal features, etiology, gut microbiome, and immune-related adverse events (irAEs). By organizing these indicators systematically, we aim to guide biomarker exploration and inform clinical treatment decisions.

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Efficacy and safety of immune checkpoint inhibitors in elderly patients with primary liver cancer: a retrospective, multicenter, real-world cohort study

Cited by 3 publications

References 39 publications

Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells

Neoadjuvant immunochemotherapy improves clinical outcomes of patients with esophageal cancer by mediating anti-tumor immunity of CD8+ T (Tc1) and CD16+ NK cells

Efficacy and safety of different PD-1 inhibitors in combination with lenvatinib in the treatment of unresectable primary liver cancer: a multicentre retrospective study

Biomarkers predicting the efficacy of immune checkpoint inhibitors in hepatocellular carcinoma

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