Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients

Zizzari, Ilaria Grazia; Filippo, Alessandra Di; Scirocchi, Fabio; Pietro, Francesca Di; Rahimi, Hassan; Ugolini, Alessio; Scagnoli, Simone; Vernocchi, Pamela; Chierico, Federica Del; Putignani, Lorenza; Rughetti, Aurelia; Marchetti, Paolo; Nuti, Marianna; Botticelli, Andrea; Napoletano, Chiara

doi:10.3390/jpm10040208

Cited by 27 publications

(42 citation statements)

References 51 publications

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“…For example, a recent study on NSCLC patients treated with nivolumab showed that lower concentration of sCTLA-4 at 3 months of clinical evaluation was associated with response. In addition to this, patients with performance status of 0 consistently maintained a lower expression of sCTLA-4 from the time of treatment initiation until 3 months of clinical evaluation indicating that sCTLA-4 can be an indicator of immune fitness in ICIs treated patients [135]. It is postulated that during ICIs treatment, sCTLA-4 might be involved in enhancing the ability of host cytotoxic T cells to attack tumor cells and thereby enhancing the antitumor effect of immunotherapy.…”

Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 78%

“…A study on nivolumab treated NSCLC patients reported that sLAG-3 was significantly increased during treatment and this increase was retained in non-responding patients. In addition to sLAG-3, other soluble mediators including sPD-1 and sPDL-2 were also increased in these patients indicating the dynamic interactive nature of LAG-3 and its role as predictive marker [135].…”

Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 87%

“…A study on 22 NSCLC patients observed that sPD-1 decreased significantly in clinically responding patients during Nivolumab treatment. In addition to this, patients with performance status of 0 had a decreased sPD-1 during treatment and these patients were found to have better immune fitness with low levels of immunosuppression [135]. Similarly, a study on 177 unresectable metastatic melanoma patients treated with anti-PD-1 showed interesting results.…”

Section: Soluble Immune Inhibitory Markers 4211 Soluble Pd-1 Pdl-1 and Pdl-2mentioning

confidence: 87%

“…However, the exact function of sTIM-3 is still unknown. A study on plasma levels of sTIM-3 in ICIs treated patients observed that NSCLC patients treated with nivolumab had a lower level of sTIM-3 at three months of clinical evaluation and this correlated with the response and longer survival of the patient [135]. Though, the study does give an indication of sTIM-3 as biomarker of response, further studies are needed to understand its dynamic nature in ICIs treatment.…”

Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 91%

“…In addition to this, soluble mediators including low PD-L1, CD137, Tim-3 and BTLA-4 in combination with low sPD-L2 are associated with favorable clinical response indicating that sPD-L2 works in synergy with other molecules to modulate the immune response. This allows understanding on the dynamic interaction of soluble immune modulators as useful biomarkers of response [135]. In addition to response prediction, a study on NSCLC patients treated with Nivolumab reported interesting results with respect to immune related adverse events.…”

Section: Soluble Immune Inhibitory Markers 4211 Soluble Pd-1 Pdl-1 and Pdl-2mentioning

confidence: 99%

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Evolving Dynamic Biomarkers for Prediction of Immune Responses to Checkpoint Inhibitors in Cancer

Raza¹,

Merhi²,

Relecom³

et al. 2021

Advances in Precision Medicine Oncology

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Immune checkpoint inhibitors (ICIs) have been approved as first or second line therapy in a large group of cancers. However, the observation of potentially long-lasting responses was restricted to limited subset of patients. Efforts have been made to identify predictive factors of response to ICIs in order to select eligible patients and to avoid exposing non-responding patients to treatment side effects. Although several biomarkers have been identified, their predictive potential remains unsatisfactory. One promising emerging approach is to focus on dynamic biomarkers to directly characterize the response and, more importantly, to identify those patients presenting an immune response failure. Several studies have shown a strong correlation between specific circulating immune cell subsets and tumor immune infiltrates. Moreover, liquid biomarkers including soluble immune checkpoint molecules have potential in predicting the modulation of the immune response under immune checkpoint blockade. In this chapter, we will discuss current advances in the study of circulatory and intra-tumoral dynamic biomarkers as predictors of responses to ICIs therapy in cancer.

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Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 78%

Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 87%

Section: Soluble Immune Inhibitory Markers 4211 Soluble Pd-1 Pdl-1 and Pdl-2mentioning

confidence: 87%

Section: Soluble Ctla-4 Tim-3 and Lag-3mentioning

confidence: 91%

Section: Soluble Immune Inhibitory Markers 4211 Soluble Pd-1 Pdl-1 and Pdl-2mentioning

confidence: 99%

See 3 more Smart Citations

Evolving Dynamic Biomarkers for Prediction of Immune Responses to Checkpoint Inhibitors in Cancer

Raza¹,

Merhi²,

Relecom³

et al. 2021

Advances in Precision Medicine Oncology

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Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD‐L1 and PD‐L2

Sato,

Komatsuda,

Inoue

et al. 2024

Head & Neck

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BackgroundPredictive biomarkers for nivolumab in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) have not yet been established.MethodsThe tumor proportion score (TPS), combined positive score (CPS), and soluble forms of programmed cell death ligand‐1 (PD‐L1) and programmed cell death ligand‐2 (PD‐L2) were retrospectively analyzed in patients with RMHNSCC treated with nivolumab.ResultsThe positivity rates for TPS (PD‐L1), CPS (PD‐L1), TPS (PD‐L2), and CPS (PD‐L2) were 73.8%, 78.2%, 56.4%, and 78.2%, respectively. Patients with high TPS (PD‐L1), CPS (PD‐L1), or CPS (PD‐L1 and PD‐L2) showed significantly prolonged progression‐free survival. Favorable overall survival was associated with high CPS (PD‐L1 and PD‐L2) and low soluble PD‐L1 and PD‐L2 levels. The expressions of tissue and soluble PD‐L1/2 were not correlated.ConclusionsOur study revealed that compared to PD‐L1 expression alone, dual expression of PD‐L1 and PD‐L2 in tissue or soluble form could be feasible biomarkers in patients with RMHNSCC who received nivolumab.

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A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

Peng¹,

Zhang

Rui³

et al. 2022

Clinical Laboratory Analysis

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Background Immunotherapy was widely used for the treatment of non‐small cell lung cancer (NSCLC). However, whether inhibition of immune checkpoints individually or simultaneously could improve the therapeutic efficacy of NSCLC remains to be investigated. Here, we explored the aberrant levels of several checkpoints and evaluated their potential diagnostic values for NSCLC. Methods Serum samples of 89 NSCLC patients and 57 healthy donors were collected from Nanjing Drum Tower Hospital between November 2019 and July 2020. Fourteen human immune checkpoints were quantified by Procarta‐Plex Human Immuno‐Oncology Checkpoint Panel. Results The expression levels of sTIM‐3, sCD137, sCD27, sLAG‐3, sIDO, sPD‐L2, sCD152, sCD80, and sPD‐1 were all significantly increased in serum of NSCLC patients. Especially, sLAG‐3 was significantly elevated in serum of NSCLC patients at early‐stage (stages I and II), TIM‐3, CD137, and CD27 were significantly higher in the advanced NSCLC patients (stages III and IV) than in the early‐stage groups. Receiver operating characteristics (ROC) results showed that except for PD‐1, all the other immune checkpoint proteins had potential diagnostic values for NSCLC. sTIM‐3 had the highest diagnostic accuracy, followed by sLAG‐3. Combining sTIM‐3, sLAG‐3, and sCD137 could increase the accuracy to a higher level. Moreover, sCD27 was correlated with NSCLC cancer type, age, sex, and disease stage, while sCD137 was correlated with age and disease stage. sTIM‐3 and sIDO were correlated with stage and age, respectively. Conclusions TIM‐3 and LAG‐3 were independent biomarkers for the early diagnosis of NSCLC. The combination of TIM‐3, LAG‐3, and CD137 could increase the diagnostic accuracy.

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Soluble Immune Checkpoints, Gut Metabolites and Performance Status as Parameters of Response to Nivolumab Treatment in NSCLC Patients

Cited by 27 publications

References 51 publications

Evolving Dynamic Biomarkers for Prediction of Immune Responses to Checkpoint Inhibitors in Cancer

Evolving Dynamic Biomarkers for Prediction of Immune Responses to Checkpoint Inhibitors in Cancer

Combined approach for predicting the efficacy of nivolumab in head and neck carcinoma by tissue and soluble expressions of PD‐L1 and PD‐L2

A comprehensive profiling of soluble immune checkpoints from the sera of patients with non‐small cell lung cancer

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