Dataset Information

Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

ABSTRACT: Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients (n = 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3+, CD4+, and CD8+ T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3+ and CD8+ T cells (p = 0.013 and p = 0.033, respectively). The pre-treatment level of exhausted T cells (CD8+PD1+Eomes+) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) (p = 0.046). In CD patients, the frequency of exhausted CD8+ T cells further decreased during treatment cycles (p = <0.0001, p = 0.0032, and p = 0.0239, respectively). In conclusion, our results suggest that the distribution of lymphocyte subsets and expression of PD-1 on T cells before treatment may help predict the outcome of anti-PD-1 treatment in NSCLC patients. In addition, assessing the initial levels of exhausted T cells as well as their decrease upon treatment may also predict response and clinical outcome.

SUBMITTER: Ottonello S

PROVIDER: S-EPMC7018763 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

Ottonello Selene S Genova Carlo C Cossu Irene I Fontana Vincenzo V Rijavec Erika E Rossi Giovanni G Biello Federica F Dal Bello Maria Giovanna MG Tagliamento Marco M Alama Angela A Coco Simona S Boccardo Simona S Vanni Irene I Ferlazzo Guido G Moretta Lorenzo L Grossi Francesco F Mingari Maria Cristina MC Carrega Paolo P Pietra Gabriella G

Frontiers in immunology 20200207

Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatmen ...[more]

PMID: 32117275

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Project description:Background: Selecting patients who potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and next-generation sequencing-based tumor mutational burden (TMB) are hot spots in studies on ICIs, but there is still confusion in the testing methods. Because blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identified blood parameters associated with the outcome of non-small cell lung cancer (NSCLC) patients with ICI monotherapy. Materials and Methods: Data from 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before the first and fifth doses of ICI treatment, we utilized Cox regression model survival analysis and receiver operating characteristic (ROC) curve analysis to assess the markers. Results: In the nivolumab cohort, the optimal cutoffs for predicting 11-month overall survival (OS) were 168.13 and 43 g/L for platelet-to-lymphocyte ratio (PLR) and albumin, respectively. When patients were grouped with PLR and albumin, a significant difference in SD-PR vs. PD rate was found between the high and low groups, which was not found when the patients were grouped by PD-L1 expression. Patients with high PLR (>168.13) or low albumin ( ? 43 g/L) before ICI had a significantly increased hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033), and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin levels. More importantly, we found that a higher PLR (>168.13) before the fifth dose of ICIs was also a prognostic biomarker, which significantly correlated with shorter OS in both the nivolumab (P = 0.046) and durvalumab cohorts (P = 0.028). Conclusions: PLR and albumin may help in the stratification of high progression and death risk groups in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have achieved promising effects in patients with non-small cell lung cancer (NSCLC). However, not all patients with NSCLC benefit from immunotherapy. There is an urgent need to explore biomarkers that could predict the survival outcomes and therapeutic efficacy in advanced NSCLC patients treated with immunotherapy. In this study, we aimed to assess the changes in peripheral blood lymphocyte subsets and their association with the therapeutic efficacy and clinical prognosis of advanced NSCLC patients treated with immunotherapy.MethodsA total of 276 patients with advanced NSCLC were enrolled. Peripheral blood lymphocyte subsets including CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells, Tregs and B cells were collected before any treatment, before immunotherapy or chemotherapy, and after 4 cycles of immunotherapy or chemotherapy. T-test was used to analyze the factors influencing lymphocyte subsets and their changes before and after therapy. Logistic regression was used to plot ROC curves and analyze the relationship between lymphocyte subsets and therapeutic efficacy. Log-rank test and Cox regression model were used to evaluate the relationship between lymphocyte subsets and progression-free survival (PFS).ResultsGender, distant metastasis, and EGFR mutation status are known to affect the proportion of peripheral blood lymphocyte subsets in patients with advanced NSCLC. The proportions of CD4+ T cells, CD8+ T cells, Tregs and B cells were found to decrease after chemotherapy as compared to the baseline. The proportion of CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, NK cells and Tregs were higher after immunotherapy than after chemotherapy. Compared to the baseline, the effective group showed significant increase in the proportions of CD4+ T cells, CD4+/CD8+ ratio, NK cells and Tregs, and the number of CD8+ T cells was significantly lower in the peripheral blood after 4 cycles of immunotherapy. On the contrary, the ineffective group did not show any significant differences in the above parameters. Baseline CD4+ T cells and NK cells were independent predictors of immunotherapy efficacy and PFS. Baseline Tregs were independent predictor of immunotherapy efficacy.ConclusionImmune checkpoint inhibitors induced changes in the proportion of peripheral blood lymphocyte subsets in patients that responded well to immunotherapy. The levels of the different lymphocyte subsets could serve as valuable predictive biomarkers of efficacy and clinical prognosis for NSCLC patients treated with immunotherapy.

Project description:BACKGROUND:Alterations in peripheral blood lymphocytes in cervical cancer have been reported, although conflicting views exist. The present study investigated the distributions of lymphocyte subsets in tumor tissue and peripheral blood samples from cervical cancer patients and precancerous lesion patients, and evaluated the correlations of lymphocyte subsets with clinicopathological and prognostic variables. METHODS:A total of 44 patients with stage IB1-IIA2 cervical cancer and 13 precancerous lesion patients were included. Lymphocytes were collected from the tumor tissue and the peripheral blood, and isolated by Lymphoprep density gradient centrifugation. The percentages of lymphocyte subsets were quantified by flow cytometry analysis, and the differences between lymphocyte subsets in the tumor tissue and peripheral blood were compared by SPSS. In addition, the relationships between lymphocyte subsets and clinicopathological and prognostic variables were analyzed. RESULTS:Our results revealed that the amount of total T lymphocytes, CD8+ T cells, granulocytes, pDCs, CD16+ monocytes and CD56high NK cells were significantly higher in the tumor tissue than in the peripheral blood in the cervical cancer patients, while those of CD4+ T cells, CD4+/CD8+ cell ratio, rdT cells, BDCA1+ mDCs, total monocytes, CD14+ monocytes, NK cells and CD56low NK cells exhibited the opposite trend (p?<?0.05). The levels of total pDCs and BDCA1+ mDCs in the peripheral blood were significantly lower in the cervical cancer patients than in the precancerous lesion patients, while the proportion of CD16+ monocytes was elevated (p?<?0.05). In addition, some lymphocyte subsets, especially CD4+ cells and CD8+ cells, and the CD4+/CD8+ cell ratio were closely associated with clinicopathological and prognostic parameters. CONCLUSIONS:These results suggested that distinct alterations in infiltrating lymphocyte subsets occurred in the tumor and were associated with clinicopathological and prognostic parameters. Systemic impairment of the immune system may occur in the antitumor response of cervical cancer patients.

Dataset Information

Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

Publications

Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

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