PD-L1 expression and smoke exposure as biomarkers for optimizing adjuvant therapy for patients with resected limited-stage small-cell lung carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu C
PROVIDER: S-EPMC10066250 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
PD-L1 expression and smoke exposure as biomarkers for optimizing adjuvant therapy for patients with resected limited-stage small-cell lung carcinoma.
Liu Chengming C Wang Zhanyu Z Zeng Qingpeng Q Zheng Sufei S Feng Xiaoli X Xue Qi Q Sun Nan N He Jie J
Genes & diseases 20220331 1
Similar Datasets
Project description:BackgroundData on efficacy of adjuvant therapy for surgically resected small cell lung cancer are scant. This study was determined to reveal the survival benefits of different adjuvant treatment modalities for limited-stage small cell lung cancer patients following surgical resection.MethodsData of patients with histologically confirmed small cell lung cancer after surgical resection were collected from November 2006 to June 2019. Survival analyses were calculated by Kaplan-Meier method, with log-rank test to evaluate statistical significance. Prognostic factors were identified by multivariate analysis using cox proportional hazards model. Further survival analysis and cox regression analysis stratified by clinicopathologic features were conducted to evaluate the survival benefits of different adjuvant treatment modalities.ResultsIn total, 153 out of 157 patients were analyzed. Multivariate analysis showed male sex, lymph node metastasis, residual tumor, VPI and non-adjuvant therapy were independently associated with poor prognosis. Subgroup analyses revealed both adjuvant chemotherapy and adjuvant chemoradiotherapy were significantly associated with superior survival for stage pT2-4 (HR=0.176, 95%CI:0.053-0.578, p=0.004; and HR=0.115, 95%CI:0.033-0.405, p=0.001) and pure SCLC patients (HR=0.182, 95%CI:0.067-0.494, p=0.001; and HR=0.181, 95%CI:0.071-0.465, p<0.001). For pN0 patients, adjuvant chemotherapy was associated with better survival (HR=0.219, 95%CI:0.054-0.891, p=0.034), while adjuvant chemoradiotherapy was associated with improved survival for pN+ patients (HR=0.324, 95%CI:0.138-0.760, p=0.010).ConclusionsFor patients without pathologic lymph node metastasis, there is a survival benefit with adjuvant chemotherapy. However, for patients with pathologic lymph node metastasis, adjuvant chemoradiotherapy might achieve a significant survival benefit. Further prospective studies are needed to validate the results.
| S-EPMC8495161 | biostudies-literature
Project description:One of the most recent advancements in NSCLC was the approval of immunotherapy in the adjuvant setting. Both atezolizumab and pembrolizumab have been approved for the use in early stage NSCLC patients post resection. As it broadens the options for our patients, multiple approvals in the same setting are generally welcomed. However, there were important differences in the two studies that led to the approvals and the data could be confusing. Here we review IMpower010, the study that led to the first approval of atezolizumab in the adjuvant setting with comparison to the Keynote-091 study evaluating pembrolizumab in the adjuvant setting, gaining the most recent FDA approval for adjuvant use in early stage NSCLC.
| S-EPMC10725831 | biostudies-literature
Project description:PurposeCurrently, adjuvant chemotherapy is recommended for patients with high risk stage I non-small cell lung cancer (NSCLC). However, identifying high risk patients remains a challenge. This study aims to identify the patient cohorts more likely to benefit from adjuvant chemotherapy based on the tumor micro-immune environment.ResultsCD8+TILs significantly associated with disease-free survival (DFS) and overall survial (OS) (p=0.002; 0.040). Patients with high risk factors may also predict shorter DFS (P=0.056). When compared together, patients with high-CD8+TILs showed better DFS than patients with low-CD8+TILs, no matter their risk factors status. There's no correlation between PD-L1 expressions and survival. PD-L1 was highly expressed in men, squamous and well differentiated carcinoma. In addition, Foxp3+TILs alone didn't show any prognostic effects, but low-Foxp3/high-CD8+TILs were associated with prolonged DFS (p=0.031).MethodsA total of 126 patients with surgically resected stage I NSCLC were included to perform immunohistochemistry of CD8+ tumor infiltrating lymphocytes (TILs), programmed death ligand-1(PD-L1) and forkhead box P3 (Foxp3)+TILs.ConclusionCD8+TILs are effective prognostic predictors. Patients with surgically resected stage I NSCLC showing low CD8+TILs could be considered for adjuvant chemotherapy, even if they have no high risk features.
| S-EPMC5325445 | biostudies-literature
Project description:Aim: Atezolizumab improved disease-free survival (DFS) versus best supportive care (BSC) as adjuvant treatment following resection and platinum-based chemotherapy for stage II-IIIA PD-L1+ NSCLC in IMpower010. Materials & methods: This cost-effectiveness study evaluated atezolizumab versus BSC (US commercial payer perspective) using a Markov model with DFS, locoregional recurrence, first- and second-line metastatic recurrence and death health states, and a lifetime time horizon with 3% annual discounting. Results: Atezolizumab provided 1.045 additional quality-adjusted life-years (QALY) at an incremental cost of $48,956, yielding an incremental cost-effectiveness ratio of $46,859/QALY. Scenario analysis showed similar findings in a Medicare population ($48,512/QALY). Conclusion: At a willingness-to-pay threshold of $150,000/QALY and an incremental cost-effectiveness ratio of $46,859/QALY, atezolizumab is cost-effective versus BSC for adjuvant NSCLC treatment.
| S-EPMC10334222 | biostudies-literature
Project description:IntroductionImmune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC.MethodsA tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression.ResultsOf 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%).ConclusionPD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.
| S-EPMC4841565 | biostudies-literature
Project description:Melanoma displays a rising incidence, and the mortality associated with metastatic form remains high. Monoclonal antibodies that block programmed death (PD-1) and PD Ligand 1 (PD-L1) network have revolutionized the history of metastatic disease. PD-L1 is expressed on several immune cells and can be also expressed on human neutrophils (PMNs). The role of peripheral blood PMNs as predictive biomarkers in anti-PD-1 therapy of melanoma is largely unknown. In this study, we aimed to determine activation status and PD-L1 expression on human neutrophils as possible novel biomarkers in stage IV melanoma patients (MPs). We found that PMNs from MPs displayed an activated phenotype and increased PD-L1 levels compared to healthy controls (HCs). Patients with lower PD-L1+ PMN frequencies displayed better progression-free survival (PFS) and overall survival (OS) compared to patients with high PD-L1+ PMN frequencies. Multivariate analysis showed that PD-L1+ PMNs predicted patient outcome in BRAF wild type MP subgroup but not in BRAF mutated MPs. PD-L1+ PMN frequency emerges as a novel biomarker in stage IV BRAF wild type MPs undergoing anti-PD-1 immunotherapy. Our findings suggest further evaluation of the role of neutrophil subsets and their mediators in melanoma patients undergoing immunotherapy.
| S-EPMC9398490 | biostudies-literature
Project description:Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.
| S-EPMC6107958 | biostudies-literature
Project description:BackgroundThe expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC.Patients and methodsTumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy.ResultsResults from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy.ConclusionsPD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.
| S-EPMC5834092 | biostudies-literature
Project description:BackgroundElevated PD-L1 expression on tumor cells, a context associated with an adaptive immune response, has been linked to the total burden of copy number variants (CNVs) in aneuploid tumors, to microsatellite instability (MSI), and to specific genomic driver lesions, including loss of PTEN, MYC amplification, and activating mutations in driver oncogenes such as KRAS and PIK3CA. Triple-negative breast cancers (TNBCs) typically have high levels of CNVs and diverse driver lesions in their genomes. Thus, there is significant interest in exploiting genomic data to develop predictive immunotherapy biomarkers for patients with TNBC.MethodsWhole tissue samples from 55 resected TNBCs were screened by immunohistochemistry (IHC) for PD-1 and PD-L1 by using validated antibodies and established scoring methods for staining of tumor and non-tumor cells. In parallel, we interrogated biopsies from each resection with DNA content flow cytometry and sorted the nuclei of diploid, tetraploid, and aneuploid cell populations. CNVs were mapped with CNV oligonucleotide arrays by using purified (>95%) tumor populations. We generated whole exome data for 12 sorted tumor samples to increase the resolution within loci of interest and to incorporate somatic mutations into our genomic signatures.Results and conclusionsPD-L1 staining was detected on tumor cells in 29 out of 54 (54%) evaluable cases and was associated with increased overall survival (P = 0.0024). High levels of PD-1 and PD-L1 (IHC ≥4) were present in 11 out of 54 (20%) and 20 out of 54 (37%) cases with staining of PD-L1 primarily on tumor cells for 17 out of 20 (85%) cases. The latter included tumors with both high (>50) and low (<20) numbers of CNVs. Notably, homozygous deletion of PTEN (n = 6) or activating mutation in PIK3CA (n = 1) was not associated with increased expression of either immune checkpoint activator in TNBC. In contrast, two treatment-naïve cases with EGFR driver amplicons had high PD-L1 tumor staining. High mutational load and predicted neoepitopes were observed in MSI+ and high CNV burden TNBCs but were not associated with high PD-L1 expression on tumor cells. Our results challenge current models of genomic-based immunotherapy signatures yet suggest that discrete genomic lesions may complement existing biomarkers to advance immune checkpoint therapies for patients with TNBC.
| S-EPMC6042255 | biostudies-literature
Project description:In recent years, immunotherapies targeting programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) have provided great hopes for patients with cancer. A successful anti-PD-1/PD-L1 therapy includes not only the elimination of immunosuppressive tumor cells but also the rejuvenation of exhausted T cells. Nevertheless, the efficacy of therapy is still low, so that biomarker-driven therapy has attracted more and more attention to identify patients who are likely to benefit from therapy and to reduce unnecessary disease progression. While many studies have focused on characteristics of tumor biopsies, biomarkers linked to T cell exhaustion and rejuvenation have just become new hot spots in drug response studies. However, no biomarker is perfect in drug response prediction currently, so there is an urgent need for other biomarkers to compensate for the deficiency. In this review, we summarize some approved and candidate biomarkers predictive of drug response before and during PD-1/PD-L1 blockade, including those characterizing responsive or suppressive tumor cells and those evaluating the T cell rejuvenation. Overall, we set up a comprehensive network of biomarkers of tumor characteristics and T cell rejuvenation, predicting drug response before and during anti-PD-1/PD-L1 therapies.
| S-EPMC6087015 | biostudies-literature