Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer

Kim, Chang Gon; Hong, Min Hee; Kim, Kyung Hwan; Seo, In-Ho; Ahn, Beung‐Chul; Pyo, Kyoung‐Ho; Synn, Chun‐Bong; Yoon, Hong In; Shim, Hyo Sup; Lee, Yong Il; Choi, Seong Jin; Lee, Yun Jeong; Kim, Ellen Janine; Kim, Youngun; Kwak, Jeong-Eun; Jung, Jinkyung; Park, Su–Hyung; Paik, Soonmyung; Shin, Eui‐Cheol

doi:10.1016/j.ejca.2020.10.028

Cited by 37 publications

(23 citation statements)

References 34 publications

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“…We found that all six lncRNAs were associated with the infiltration of various interrelated immune cells. Considerable evidence suggests that CD8+ T cell subsets play important roles in tumor control, as reflected by the relationship between the number of CD8+ T cells in the tumor before treatment and the response to PD-1 therapy ( Kim et al, 2021 ). After circulating CD8+ T cells infiltrate tumor tissues, they are activated by tumor antigens to transform into effector CD8+ T cells which kill tumor cells.…”

Section: Discussionmentioning

confidence: 99%

CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

Yang

2021

Front. Cell Dev. Biol.

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The prognosis of patients with endometrial cancer (EC) is closely associated with immune cell infiltration. Although abnormal long non-coding RNA (lncRNA) expression is also linked to poor prognosis in patients with EC, the function and action mechanism of immune infiltration-related lncRNAs underlying the occurrence and development of EC remains unclear. In this study, we analyzed lncRNA expression using The Cancer Genome Atlas and clinical data and identified six lncRNAs as prognostic markers for EC, all of which are associated with the infiltration of immune cell subtypes, as illustrated by ImmLnc database and ssGSEA analysis. Real-time quantitative polymerase chain reaction showed that CDKN2B-AS1 was significantly overexpressed in EC, whereas its knockdown inhibited the proliferation and invasion of EC cells and the in vivo growth of transplanted tumors in nude mice. Finally, we constructed a competing endogenous RNA regulatory network and conducted Gene Ontology enrichment analysis to elucidate the potential molecular mechanism underlying CDKN2B-AS1 function. Overall, we identified molecular targets associated with immune infiltration and prognosis and provide new insights into the development of molecular therapies and treatment strategies against EC.

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Section: Discussionmentioning

confidence: 99%

CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

Yang

2021

Front. Cell Dev. Biol.

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“… 54–56 The analysis of the currently suggested biomarkers for PD-1 blockade, such as PD-L1 expression, tumor mutation burden, pre-existing T cell infiltration, and transcription signatures, necessitates the collection of tissue specimens, which is apparently associated with a higher risk of procedure-related comorbidity and mortality, especially in NSCLC patients. 27 57 Considering these aspects, blood-based biomarker analysis can be a valuable tool for serial immune monitoring. We anticipate that our findings can be validated by matching tumor samples with blood samples in future clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…The tumor proportion score was determined for the positivity of PD-L1 expression on tumor cells as described previously. 27 PD-L1 expression in freshly collected surgically resected tumor tissues was determined by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

Distinct exhaustion features of T lymphocytes shape the tumor-immune microenvironment with therapeutic implication in patients with non-small-cell lung cancer

Kim

et al. 2021

J Immunother Cancer

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BackgroundReinvigoration of T-cell exhaustion with antibodies has shown promising efficacy in patients with non-small-cell lung cancer (NSCLC). However, the characteristics of T-cell exhaustion with regard to tumor-infiltrating lymphocytes (TILs) are poorly elucidated in NSCLC. Here, we investigated the exhaustion status of TILs in NSCLC patients at the intraindividual and interindividual levels.MethodsWe obtained paired peripheral blood, normal adjacent tissues, peritumoral tissues, and tumor tissues from 96 NSCLC patients. Features of T-cell exhaustion were analyzed by flow cytometry. T cells were categorized according to their programmed cell death-1 (PD-1) expression (PD-1high, PD-1int, and PD-1neg cells). Patients were classified based on the presence or absence of discrete PD-1high CD8+ TILs. Production of effector cytokines by CD8+ TILs was measured after T-cell stimulation with or without antibodies against immune checkpoint receptors.ResultsProgressive T-cell exhaustion with marked expression of exhaustion-related markers and diminished production of effector cytokines was observed in PD-1high CD8+ TILs compared with PD-1int and PD-1neg CD8+ TILs. Patients with distinct PD-1high CD8+ TILs (PD-1high expressers) exhibited characteristics associated with a favorable anti-PD-1 response compared with those without these lymphocytes (non-PD-1high expressers). Combined inhibition of dual immune checkpoint receptors further restored effector cytokine production by CD8+ TILs following T-cell stimulation. PD-1high CD8+ T lymphocyte populations in the peripheral blood and tumors were significantly correlated.ConclusionsT-cell exhaustion was differentially regulated among individual patients and was prominent in a subgroup of NSCLC patients who may benefit from PD-1 blockade or combined blockade of other immune checkpoint receptors.

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“…In recent years, immunotherapy for NSCLC has been developing rapidly, especially for PD-1/PD-L1 inhibitors [ 38 – 42 ]. While tumor immunotherapy has achieved satisfactory anti-tumor efficacy, predictive indicators related to therapeutic efficacy and prognosis have also been gradually reported [ 16 – 19 , 43 ]. Based on the aforementioned reports on immune predictive indicators, we designed the present study in order to comprehensively evaluate the impact of immune-related indicators or immune grouping methods on the therapeutic efficacy and prognosis of NSCLC [ 16 – 19 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Immune subgroup analysis for non-small cell lung cancer may be a good choice for evaluating therapeutic efficacy and prognosis

Tian

Wang

Wen

et al. 2021

Aging

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Due to its effectiveness, cancer immunotherapy has attracted widespread attention from clinicians and scientific researchers. Numerous studies have proven that effective stratification of cancer patients would promote the personalized application of immunotherapy. Therefore, we used the transcriptome data of nearly 1,000 patients with non-small cell lung cancer (NSCLC) to construct a new immune subgroup. We found that the new immune subgroup, named cluster 2, was a mixture of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and showed poor overall survival, which was further verified in the independent validation set. Immune infiltration correlation analysis showed that the Mast cell type and its status subdivisions had a predictive effect on the prognosis of NSCLC, especially in LUAD. Phenotypic analysis suggested that epithelial-mesenchymal transition (EMT) was positively correlated with immunosuppression, supporting the correlation between tumor phenotype and immune background. Although immune subtypes failed to significantly distinguish the progression-free survival (PFS) of immunotherapy patients, they showed the expected trend; the sample size needs to be further expanded for verification. In addition, some results indicated that the two cancer types, LUAD and LUSC, might require independent analyses.

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Dynamic changes in circulating PD-1+CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer

Cited by 37 publications

References 34 publications

CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

CDKN2B-AS1 Promotes Malignancy as a Novel Prognosis-Related Molecular Marker in the Endometrial Cancer Immune Microenvironment

Distinct exhaustion features of T lymphocytes shape the tumor-immune microenvironment with therapeutic implication in patients with non-small-cell lung cancer

Immune subgroup analysis for non-small cell lung cancer may be a good choice for evaluating therapeutic efficacy and prognosis

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