T lymphocytes related biomarkers for predicting immunotherapy efficacy in non‑small cell lung cancer (Review)

Wei, Xuedong; Gu, Ling; Heng, Wei

doi:10.3892/ol.2020.12350

Cited by 9 publications

(6 citation statements)

References 95 publications

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“…The tumor infiltration of T lymphocytes has been previously proposed as a predictive biomarker for ICI therapy outcomes (44). Our study found that upon treatment with ICIs, the plasma proteome is enriched with proteins associated with enhanced T cell activity and proliferation, an effect detectable in both R and NR populations.…”

Section: Discussionmentioning

confidence: 99%

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Bar,

Leibowitz,

Reinmuth

et al. 2024

Preprint

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IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network with CD8A serving as a central hub, suggesting T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and potential biomarkers for outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Bar,

Leibowitz,

Reinmuth

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The tumor infiltration of T lymphocytes has been previously proposed as a predictive biomarker for ICI therapy outcomes ( 47 ). Our study found that upon treatment with ICIs, the plasma proteome is enriched with proteins associated with enhanced T cell activity and proliferation, an effect detectable in both R and NR populations.…”

Section: Discussionmentioning

confidence: 99%

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Bar,

Leibowitz,

Reinmuth

et al. 2024

Front. Immunol.

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IntroductionImmune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes in blood plasma to gain a better understanding of treatment response and resistance.MethodsPre-treatment (T0) and on-treatment (T1) plasma samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was profiled using aptamer-based technology to quantify approximately 7000 plasma proteins per sample. Proteins displaying significant fold changes (T1:T0) were analyzed further to identify associations with clinical outcomes using clinical benefit and overall survival as endpoints. Bioinformatic analyses of upregulated proteins were performed to determine potential cell origins and enriched biological processes.ResultsThe levels of 142 proteins were significantly increased in the plasma of NSCLC patients following ICI-based treatments. Soluble PD-1 exhibited the highest increase, with a positive correlation to tumor PD-L1 status, and, in the ICI monotherapy dataset, an association with improved overall survival. Bioinformatic analysis of the ICI monotherapy dataset revealed a set of 30 upregulated proteins that formed a single, highly interconnected network, including CD8A connected to ten other proteins, suggestive of T cell activation during ICI treatment. Notably, the T cell-related network was detected regardless of clinical benefit. Lastly, circulating proteins of alveolar origin were identified as potential biomarkers of limited clinical benefit, possibly due to a link with cellular stress and lung damage.ConclusionsOur study provides insights into the biological processes activated during ICI-based therapy, highlighting the potential of plasma proteomics to identify mechanisms of therapy resistance and biomarkers for outcome.

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“…Meanwhile, CD4 TILs were identified as significant predictors when evaluated in tumor stroma rather than tumor cell nests [ 8 ]. In a recent review, Wei et al suggested that CD8 TILs mediate stronger antitumor responses than CD4 TILs [ 9 ]. However, previous reports didn’t focus on NSCLC patients who received immunotherapy as 2nd or more over lines.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer

et al. 2023

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Aim Tumor-infiltrating lymphocytes (TILs) in the tumor and stroma are expected to accurately predict the efficacy of programmed death-1 (PD-1) blockade therapy. However, little is known about the prognostic significance of TILs in first-line PD-1 therapy. We assessed TILs in patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with pembrolizumab in the palliative setting. Methods Multiplex immunohistochemistry staining of TILs (CD4, CD8, Foxp3, and PD-1) and immunohistochemical staining of CK and PD-L1 in the tumor and stroma was performed in tumor specimens of 107 NSCLC patients and correlated with clinical outcomes, as a single-center retrospective study. TILs and programmed death ligand-1 (PD-L1) were assessed on biopsies (N = 93) or surgical resections (N = 14) before first-line pembrolizumab. Results A low number of stromal CD4 TILs were significantly associated with bone metastasis and poor performance status (PS). The median progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with a high number of stromal CD4 TILs (336 days and 731 days, respectively) than in those with low infiltration (204 days and 333 days, respectively). Patients with a high number of intratumoral CD8 TILs (731 days) yielded significantly better OS than those with low infiltration (333 days), but not for PFS. Multivariate analysis confirmed that stromal CD4 TILs were independent predictors of PFS, but not OS. Furthermore, intratumoral CD8 TILs were independent predictors of better OS. In the survival analysis of key subgroups, stromal CD4 TILs were identified as significant predictors of survival in patients with non-adenocarcinomatous histology and PD-L1 ≥ 50%. Conclusion Stromal CD4 TILs were identified as a significant marker for predicting the PFS after pembrolizumab therapy, especially in patients with non-adenocarcinoma and high PD-L1 expression. In addition, intratumoral CD8 TILs were identified as significant predictors of OS.

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T lymphocytes related biomarkers for predicting immunotherapy efficacy in non‑small cell lung cancer (Review)

Cited by 9 publications

References 95 publications

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Biological insights from plasma proteomics of non-small cell lung cancer patients treated with immunotherapy

Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer

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