Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Hou, Wanting; Zhou, Xiaohan; Yi, Cheng; Zhu, Hong

doi:10.3389/fonc.2021.604227

Cited by 14 publications

(11 citation statements)

References 74 publications

(86 reference statements)

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“…Worse than this, the application of anti-PD-1/PD-L1 in SCLC patients is further shadowed by the life-threatening immunotoxicities. Hence, it is of great importance to identify factors to predict the potential responder to anti-PD-1/PD-L1 inhibitor combined with chemotherapy in SCLC patients (25).…”

Section: Discussionmentioning

confidence: 99%

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

et al. 2021

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ObjectivesThe objective of this study is to evaluate whether PIV (Pan-Immune-Inflammation Value) and PILE [a score derived from PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)] can predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in patients with extensive-stage (ES) small cell lung cancer (SCLC).MethodsA total of 53 patients with ES-SCLC in the control group of clinical trial (NCT03041311) were included in this study. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE scores were composited based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Moreover, the predictive ability of PIV and PILE was validated in an independent real-world group consisting of 84 patients.ResultsPatients in the low PIV group (PIV < median) had longer progression-free survival (PFS) and overall survival (OS) than those in the high PIV group (PIV ≥ median), along with the HR, which was 2.157 and 2.359, respectively (PFS HR 95% CI: 1.181–3.940, p = 0.012; OS HR 95% CI: 1.168–4.762, p = 0.020). High PILE score was observed relating to worse treatment efficacy (disease control rate (DCR): 84.21% vs. 100%, p = 0.047; durable clinical benefit (DCB) rate: 10% vs. 48.5%, p = 0.060) and poor clinical outcome (median PFS: 4.75 vs. 5.53 m, p = 0.043; median OS: 7.13 vs. 15.93 m, p = 0.002). Similar results were obtained about the predictive and prognostic abilities of PIV and PILE scores in the validation group.ConclusionsHigh PIV and high PILE were correlated with worse clinical outcomes in ES-SCLC patients treated with anti-PD-1/PD-L1 inhibitor combined with chemotherapy, reflecting that PIV and PILE might be useful to identify patients unlikely to benefit from anti-PD-1/PD-L1 therapy.

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Section: Discussionmentioning

confidence: 99%

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

et al. 2021

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“…However, the adverse effects and high cost pose an obstacle to its application. Therefore, screening out the patients who are really suitable for immunotherapy is required ( Hou et al, 2021 ). Owing to the heterogeneity of tumors, single-cell sequencing analysis is becoming popular.…”

Section: Discussionmentioning

confidence: 99%

Insights into the roles and driving forces of CCT3 in human tumors

Song²,

Liu³

et al. 2022

Front. Pharmacol.

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CCT3 played a key role in many cancers. This study aimed to further explore the characteristics of CCT3 from a pan-cancer perspective and reveal the driving forces for CCT3. By bioinformatic analysis, we found that the mRNA and protein levels of CCT3 were abnormally elevated in most tumor types and were correlated with poor prognosis. Single-cell sequencing data indicated an abnormal increase of CCT3 expression in both malignant cells and multiple immune cells. In the tumor microenvironment, CCT3 expression was negatively relevant with immune cell infiltration and immune checkpoint genes expression. In colon cancer, knockdown of CCT3 inhibited cell proliferation. Gene set enrichment analysis showed that CCT3 may be oncogenic by regulating amino acid metabolism. Furthermore, we predicted sensitive drugs for CCT3 by virtual screening and sensitivity analysis. Many driver genes such as TP53 and KRAS were essential for CCT3 overexpression. Epigenetic factors, enhancers in particular, were also critical for CCT3 expression. Additionally, we constructed the lncRNA/circRNA-miRNA-CCT3 regulatory network. Collectively, CCT3 had the potential to be a diagnostic and prognostic biomarker for multiple tumor types. CCT3 expression was relevant with an immunosuppressive tumor microenvironment. CCT3 could be a new molecular target for colon cancer. Both genetic and epigenetic factors were responsible for CCT3 expression in tumors.

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“…The main targets of the ICIs include cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1). Monoclonal antibodies, including anti-PD-L1 inhibitors (e.g., atezolizumab, durvalumab, and avelumab), anti-PD-1 inhibitors (e.g., pembrolizumab and nivolumab), and CTLA4 receptor inhibitors (e.g., ipilimumab and tremelimumab), have been approved by the FDA for several solid tumor treatments [ 30 , 31 ]. ICI monoclonal antibodies, as single drugs or combination strategies, were studied in PDAC clinical trials [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

Section: Status and Dilemma Of Immunotherapy For Pdacmentioning

confidence: 99%

“…Studies on ICIs and their use in a combined strategy account for the majority of the PDAC clinical research. ICIs release the inhibitory brakes in T cells, which strongly activates the immune system and induces antitumor immune reactions [ 30 , 31 ]. The first reported ICI in a PDAC clinical trial was ipilimumab, a CTLA-4 inhibitor.…”

Section: Status and Dilemma Of Immunotherapy For Pdacmentioning

confidence: 99%

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy

2022

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Immunotherapy has dramatically changed prognosis for patients with malignant tumors. However, as a non-immunogenic tumor, pancreatic ductal adenocarcinoma (PDAC) has a low response to immunotherapy. Factors that contribute to the inefficiency of PDAC immunotherapy include the tumor microenvironment (TME) and its dense stroma, which acts as a barrier for drug delivery and immune cell infiltration. Recent studies have shown that nanoparticle-based therapeutic strategies have more promising applications in improving drug delivery and reversing the immunosuppressive TME for PDAC. Therefore, nanomaterial-based therapeutic approaches are expected to enhance the effectiveness of immunotherapy and improve prognosis of patients with PDAC. Here, we outline the status and dilemma of PDAC immunotherapy, and summarize the latest advances in nanoparticle-based treatment strategies to enhance the efficacy of PDAC immunotherapy.

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Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

Cited by 14 publications

References 74 publications

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients

Insights into the roles and driving forces of CCT3 in human tumors

Nanoparticle-Based Therapeutic Strategies for Enhanced Pancreatic Ductal Adenocarcinoma Immunotherapy

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