ArticleFrontiers in oncology2021
Low Infiltration of CD8+ PD-L1+ T Cells and M2 Macrophages Predicts Improved Clinical Outcomes After Immune Checkpoint Inhibitor Therapy in Non-Small Cell Lung Carcinoma.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 30 citations in OpenAlex.
- Spatial single-cell proteotyping reveals immunotherapy-resistant features within the complex tumor microenvironment of metastatic NSCLC.The Journal of clinical investigation · 2026Article
- Article
- An IHC-derived TLS-CD8-macrophage immune niche score predicts major pathological response to neoadjuvant chemoimmunotherapy in resectable NSCLC.Frontiers in immunology · 2026Article
- TGFβ1 and SMAD3 Expression Are Associated With Survival After the Immune Checkpoint Inhibitor Therapy for Small Cell Lung Cancer.Cancer reports (Hoboken, N.J.) · 2025Article
- Exploring predictive biomarkers of efficacy and survival with nivolumab treatment for unresectable/recurrent esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2025Article
- LILRB2 blockade facilitates macrophage repolarization and enhances T cell-mediated antitumor immunity.Journal for immunotherapy of cancer · 2025Article
- Targeting the Tumor Microenvironment in EGFR-Mutant Lung Cancer: Opportunities and Challenges.Biomedicines · 2025Review
- PD-L1International journal of molecular sciences · 2024Article
- Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy.Heliyon · 2024Review
- Potential association of HSPD1 with dysregulations in ribosome biogenesis and immune cell infiltration in lung adenocarcinoma: An integrated bioinformatic approach.Cancer biomarkers : section A of Disease markers · 2024Article
- Recent advancements in the B7/CD28 immune checkpoint families: new biology and clinical therapeutic strategies.Cellular & molecular immunology · 2023Review
- Associations of immune checkpoint inhibitor therapy efficacy with clinical parameters and tumor‑infiltrating CD68‑positive cell counts in patients with EGFR‑mutant non‑small cell lung cancer.Molecular and clinical oncology · 2023Article
- Current literature review on the tumor immune micro-environment, its heterogeneity and future perspectives in treatment of advanced non-small cell lung cancer.Translational lung cancer research · 2023Review
- Comparison of PD-L1 expression in squamous cell cancer of unknown primary and oropharyngeal squamous cell carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Article
- Prediction of CD3 T cells and CD8 T cells expression levels in non-small cell lung cancer based on radiomic features of CT images.Frontiers in oncology · 2023Article
- Infiltration of a Unique CD8Journal of hepatocellular carcinoma · 2023Article
- Sinus metastasis of lung adenocarcinoma: a case report.Frontiers in medicine · 2023Article
- Cell Therapy with Human Reprogrammed CD8International journal of molecular sciences · 2022Article
- Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy.Frontiers in immunology · 2022Review
- Extremely high infiltration of CD8Frontiers in oncology · 2022Article
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8 authors at 5 institutions in 1 country.
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Abstract
backgroundMany clinical studies have shown that patients with non-small cell lung carcinoma (NSCLC) can benefit from immune checkpoint inhibitor (ICI) therapy; however, PD-L1 and tumor mutation burden (TMB), which are recommended by the NCCN guidelines, are still insufficient in predicting the response to and prognosis of immunotherapy. Given the widespread use of ICIs, it is important to find biomarkers that can predict immunotherapy outcomes in NSCLC patients, and the exploration of additional effective biomarkers for ICI therapy is urgently needed.
methodsA total of 33 stage II-IV NSCLC patients were included in this study. We analyzed immune markers in biopsy and surgical tissue resected from these patients before treatment with ICIs. We examined the infiltration of immune cells and expression of PD-L1 in immune cells using fluorescent multiplex immunohistochemistry (mIHC) stained with CD8/CD68/CD163/PD-L1 antibodies.
resultsIn this cohort, we observed that the levels of CD8+ T cells, CD8+PD-L1+ T cells, and CD68+CD163+ M2 macrophages in the total region were independent prognostic factors for progression-free survival (PFS) in NSCLC patients treated with ICIs (HR=0.04, P=0.013; HR=17.70, P=0.026; and HR=17.88, P=0.011, respectively). High infiltration of CD8+ T cells and low infiltration of CD8+PD-L1+ T cells throughout the region were correlated with prolonged PFS (P=0.016 and P=0.02, respectively). No statistically significant difference was observed for CD68+CD163+ M2 macrophages. The joint parameters CD8+ high/CD8+PD-L1+ low, CD8+ high/CD68+CD163+ low and CD8+PD-L1+ low/CD68+CD163+ low predicted better PFS than other joint parameters (P<0.01, P<0.01, and P<0.001, respectively), and they also demonstrated stronger stratification than single biomarkers. The response rate of patients with high infiltration of CD8+ T cells was significantly higher than that of those with low infiltration (P<0.01), and the joint parameters CD8+/CD8+PD-L1+ and CD8+/CD68+CD163+ also demonstrated stronger stratification than single biomarkers.
conclusionsThis retrospective study identified the predictive value of CD8+PD-L1+ T cells, CD8+ T cells, and CD68+CD163+ M2 macrophages in NSCLC patients who received ICIs. Interestingly, our results indicate that the evaluation of joint parameters has certain significance in guiding ICI treatment in NSCLC patients.
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