Dataset Information

Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.

ABSTRACT:

Background

The establishment of biomarkers that can be used to predict the response to immunotherapy for malignancy is extremely important. In particular, noninvasive analysis of immune cells from peripheral blood before treatment has gained increased attention, and natural killer (NK) cell activity has been shown to be related to treatment response. Here, we aimed to confirm the relationship between the response to immunotherapy and NK cell activity.

Methods

In this prospective observational study, patients with advanced NSCLC who were scheduled for immunotherapy from October 2018 to December 2019 were enrolled. Baseline NK cell activity was compared according to the best clinical response to immunotherapy.

Results

A total of 54 patients with advanced NSCLC were enrolled, and 34 patients were analyzed. The baseline NK cell activity was significantly higher in the non-PD group than in the PD group (P = 0.002). At the cutoff level of ≥1200 pg/mL, baseline NK cell activity yielded a sensitivity of 80% and a specificity of 68.4% in predicting the response to immunotherapy (AUC = 0.8, P < 0.003). The median progression-free survival (PFS) was significantly better in the high NK group (P = 0.003), and correlation between baseline NK cell activity and PFS was also confirmed (r = 0.517, P = 0.002).

Conclusions

Baseline NK cell activity was related to the response to immunotherapy and the PFS. We suggest that NK cell activity from peripheral blood before immunotherapy is a noninvasive, simple, and novel way to predicting the treatment response in patients with NSCLC.

Key points

SIGNIFICANT FINDINGS OF THE STUDY: The response to immunotherapy was significantly better in patients with high baseline NK cell activity, and there was a significant correlation between baseline NK cell activity and PFS. What this study adds This study demonstrates the efficacy of baseline NK cell activity from peripheral blood as a biomarker for predicting immunotherapy response.

SUBMITTER: Choi MG

PROVIDER: S-EPMC7606014 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.

Choi Myeong Geun MG Kim Yeon Joo YJ Lee Jae Cheol JC Rho Jin Kyung JK Choi Chang-Min CM

Thoracic cancer 20201005 11

<h4>Background</h4>The establishment of biomarkers that can be used to predict the response to immunotherapy for malignancy is extremely important. In particular, noninvasive analysis of immune cells from peripheral blood before treatment has gained increased attention, and natural killer (NK) cell activity has been shown to be related to treatment response. Here, we aimed to confirm the relationship between the response to immunotherapy and NK cell activity.<h4>Methods</h4>In this prospective o ...[more]

PMID: 33017518

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Project description:Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatments over the last 10 years, with even increasing indications in many neoplasms. Non-small cell lung cancer (NSCLC) is considered highly immunogenic, and ICIs have found a wide set of applications in this area, in both early and advanced lines of treatment, significantly changing the prognosis of these patients. Unfortunately, not all patients can benefit from the treatment, and resistance to ICIs can develop at any time. In addition to T lymphocytes, which are the major target, a variety of other cells present in the tumor microenvironment (TME) act in a complex cross-talk between tumor, stromal, and immune cells. An imbalance between activating and inhibitory signals can shift TME from an "anti-" to a "pro-tumorigenic" phenotype and vice versa. Natural killer cells (NKs) are able to recognize cancer cells, based on MHC I (self and non-self) and independently from antigen presentation. They represent an important link between innate and adaptive immune responses. Little data are available about the role of pro-inflammatory NKs in NSCLC and how they can influence the response to ICIs. NKs express several ligands of the checkpoint family, such as PD-1, TIGIT, TIM-3, LAG3, CD96, IL1R8, and NKG2A. We and others have shown that TME can also shape NKs, converting them into a pro-tumoral, pro-angiogenic "nurturing" phenotype through "decidualization." The features of these NKs include expression of CD56, CD9, CD49a, and CXCR3; low CD16; and poor cytotoxicity. During ICI therapy, tumor-infiltrating or associated NKs can respond to the inhibitors or counteract the effect by acting as pro-inflammatory. There is a growing interest in NKs as a promising therapeutic target, as a basis for adoptive therapy and chimeric antigen receptor (CAR)-NK technology. In this review, we analyzed current evidence on NK function in NSCLC, focusing on their possible influence in response to ICI treatment and resistance development, addressing their prognostic and predictive roles and the rationale for exploiting NKs as a tool to overcome resistance in NSCLC, and envisaging a way to repolarize decidual NK (dNK)-like cells in lung cancer.

Project description:BackgroundCurrently, immunotherapy is widely used in the treatment of various stages of non-small cell lung cancer. According to clinical experience and results of previous studies, immunotherapy as neoadjuvant therapy seems to exhibit better efficacy against early resectable non-small cell lung cancer as compared to advanced lung cancer, which is often defined as unresectable non-small cell lung cancer. However, this observation has not been established in clinical studies. This systematic review aimed to evaluate the efficacy of immunotherapy in early and late lung cancer, wherein objective response rate (ORR) and disease control rate (DCR) were used as evaluation indexes. The present study also evaluated the safety of immunotherapy in early and late lung cancer, wherein the rate of treatment-related adverse reactions (TRAEs) was used as an indicator.MethodsElectronica databases, including PubMed, Cochrane Library, Embase, and other databases, were searched to identify relevant studies. Besides this, all the available reviews, abstracts, and meeting reports from the main international lung cancer meetings were searched manually. ORR, DCR, and TRAEs were extracted as the primary outcomes.ResultsA total of 52 randomized controlled trials involving 13,660 patients were shortlisted. It was observed that immunotherapy alone significantly improved DCR in early lung cancer in comparison to advanced lung cancer. Importantly, the improvement in ORR was not to the same extent as reported in the case of advanced lung cancer. The combination of immunotherapy with other therapies, especially immunochemotherapy, significantly improved ORR and DCR in early lung cancer. In terms of safety, immunotherapy either alone or in combination with other therapies exhibited a better safety profile in early lung cancer than in advanced lung cancer.ConclusionsAltogether, the benefits of immunotherapy in early lung cancer appeared to be better than those observed in advanced lung cancer, especially with the regard to the regimen of immunotherapy in combination with chemotherapy. In terms of safety, both immunotherapy alone and its combination with chemotherapy were found to be safer in early lung cancer as compared to advanced lung cancer.

Project description:Background The high expression of programmed cell death 1-ligand 1 (PD-L1) is a valid biological indicator of the therapeutic benefit of pembrolizumab in non-small cell lung cancer (NSCLC) patients. However, the response rate of NSCLC patients with positive PD-L1 expression to anti-PD-1/PD-L1 therapy is still low. Methods From January 2019 to January 2021, a retrospective study was conducted at the Fujian Medical University Xiamen Humanity Hospital. In total, 143 patients with advanced NSCLC were treated with immune checkpoint inhibitors, and the efficacy of the treatment [complete remission (CR), partial remission (PR), stable disease (SD), or progression disease (PD)] was evaluated. Patients with a CR and PR were defined as an objective response (OR) group (n=67), and the other patients were defined as a control group (n=76). The differences in the circulating tumor DNA (ctDNA) and clinical features between the 2 groups were compared, and the receiver operating characteristic (ROC) curve was used to analyze the value of ctDNA in predicting the failure to achieve an OR after immunotherapy in patients with NSCLC, and a multivariate regression analysis was conducted to analyze the factors affecting the OR after immunotherapy in NSCLC patients. R4.0.3 statistical software (Ross Ihaka Robert Gentleman, New Zealand) was used to establish and verify the prediction model of OR after immunotherapy in NSCLC patients. Results CtDNA was valuable in predicting the non-OR of patients with NSCLC after immunotherapy, and the area under the curve was 0.750 [95% CI: 0.673–0.828, P<0.001]. CtDNA <3.72 ng/µL can be used to predict which NSCLC patients will achieve objective remission after immunotherapy (P<0.001). Based on the regression model, a prediction model was established. The data set was randomly divided into the training set and validation set. The sample size of the training set was 72 and that of the validation set was 71. The area under the ROC curve of the training set was 0.850 (95% CI: 0.760–0.940), and that of the validation set was 0.732 (95% CI: 0.616–0.847). Conclusions CtDNA was valuable in predicting the efficacy of immunotherapy in NSCLC patients.

Dataset Information

Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.

Background

Methods

Results

Conclusions

Key points

Publications

Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer.

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