Effect of Neoadjuvant Therapy on Tumor Tissue PD-L1 and VISTA Expression Levels in Non-Small-Cell Lung Cancer

Akdoğan, Orhun; Sütçüoğlu, Osman; Öğüt, Betül; Akyürek, Nalân; Özdemir, Nuriye; Özet, Ahmet; Yazıcı, Ozan

doi:10.2217/imt-2021-0338

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…For patients with a CPS between 1 and 10, radiotherapy could be added to the treatment plan to improve the immune microenvironment, promote tumor antigen release, and upregulate PD-L1 expression. 55 Our study revealed that the drug acquisition cost of serplulimab accounts for 91.91% of the total incremental cost, indicating that the cost of obtaining serplulimab is significantly higher than that of chemotherapy drugs. Lowering the price of serplulimab could significantly enhance its cost-effectiveness, a finding supported by our model's one-way deterministic sensitivity analysis results.…”

Section: Discussionmentioning

confidence: 74%

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Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China

Lin,

Zhou,

et al. 2023

Ther Adv Med Oncol

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Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China’s GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China

Lin,

Zhou,

et al. 2023

Ther Adv Med Oncol

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“…Radiotherapy upregulates the expression of PD‐1 in NK cells and PD‐L1 in NPC cells, blocks the anti‐tumor function of NK cells, and reduces NPC cells recognition, resulting in tumor cells evading immune surveillance (Makowska et al, 2021). Neoadjuvant therapy, including chemotherapy and radiotherapy, was found to increase the expression of PD‐L1 and VISTA in non‐small‐cell lung cancer (Akdoğan et al, 2022). Whole‐body irradiation in mice resulted in significantly elevated PD‐1 expression in both CD4+ and CD8+ T cell populations and persisted until the 4th week, affecting T cell activation (Li et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy upregulated immune checkpoints contribute to the development of second primary OSCC

Wang¹,

Wang²,

J³

et al. 2023

Oral Diseases

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ObjectivesRadiation injury is common after radiotherapy for head and neck cancer. Radiotherapy can reshape the immune microenvironment and cause immunosuppression, including dysregulation of immune checkpoints (ICs). However, the relationship between oral ICs expression after radiation and the development of second primary tumors is unclear.MethodsClinical specimens of second primary oral squamous cell carcinoma after radiotherapy (s‐OSCC) and primary OSCC (p‐OSCC) were collected. The expression and prognostic value of PD‐1, VISTA, and TIM‐3 were analyzed using immunohistochemistry. To further clarify the relationship between radiation and ICs alteration, a rat model was constructed to explore the spatiotemporal changes of ICs in the oral mucosa after radiation.ResultsIn carcinoma tissue, the expression of TIM‐3 was higher in s‐OSCC than in p‐OSCC, while the expression of PD‐1 and VISTA was similar between the groups. In para‐carcinoma tissue, the expression of PD‐1, VISTA, and TIM‐3 was higher in s‐OSCC. High ICs expression was associated with poor survival. In the rat model, ICs were locally upregulated in the irradiated tongue. Moreover, there was a bystander effect, in which the ICs were also upregulated in the unirradiated site.ConclusionRadiation may upregulate ICs expression in oral mucosa and contribute to the development of s‐OSCC.

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“…Recent observations have shown that higher VISTA expression is related to better clinical results, whereas PD-L1 expression is associated with worse outcomes in patients with malignant cell carcinoma [17]. VISTA is mostly expressed on TME immune cells in most human malignancies and mouse models, while it has also been found in lung, kidney, and colorectal tumor cells, endometrial tissue, and human ovaries [19,20,43,47,[51][52][53][54][55][56][57][58]. Tumor immunity is impacted by VISTA in both positive and negative ways.…”

Section: Introductionmentioning

confidence: 99%

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

Olbromski,

Mrozowska,

Piotrowska

et al. 2024

Cancer Immunol Immunother

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A checkpoint protein called the V-domain Ig suppressor of T cell activation (VISTA) is important for controlling immune responses. Immune cells that interact with VISTA have molecules, or receptors, known as VISTA receptors. Immune system activity can be modified by the interaction between VISTA and its receptors. Since targeting VISTA or its receptors may be beneficial in certain conditions, VISTA has been studied in relation to immunotherapy for cancer and autoimmune illnesses. The purpose of this study was to examine the expression levels and interactions between VISTA and its receptors, VSIG3 and PSGL-1, in breast cancer tissues. IHC analysis revealed higher levels of proteins within the VISTA/VSIG3/PSGL-1 axis in cancer tissues than in the reference samples (mastopathies). VISTA was found in breast cancer cells and intratumoral immune cells, with membranous and cytoplasmic staining patterns. VISTA was also linked with pathological grade and VSIG3 and PSGL-1 levels. Furthermore, we discovered that the knockdown of one axis member boosted the expression of the other partners. This highlights the significance of VISTA/VSIG3/PSGL-1 in tumor stroma and microenvironment remodeling. Our findings indicate the importance of the VISTA/VSIG3/PSGL-1 axis in the molecular biology of cancer cells and the immune microenvironment.

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Effect of Neoadjuvant Therapy on Tumor Tissue PD-L1 and VISTA Expression Levels in Non-Small-Cell Lung Cancer

Cited by 4 publications

References 31 publications

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China

Cost-effectiveness analysis of serplulimab in combination with cisplatin plus 5-fluorouracil chemotherapy compared to cisplatin plus 5-fluorouracil chemotherapy as first-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China

Radiotherapy upregulated immune checkpoints contribute to the development of second primary OSCC

The VISTA/VSIG3/PSGL-1 axis: crosstalk between immune effector cells and cancer cells in invasive ductal breast carcinoma

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