Interleukin 8 in plasma is an efficacy marker for advanced non-small cell lung cancer treated with hypofractionated radiotherapy and PD-1 blockade

Kang, Pengyuan; Liú, Dan; Li, Lin; Guo, Xiyuan; Ye, Yingchun; Li, Yunfei; Jiang, Qin; Lin, Sheng; Yuan, Qing

doi:10.1016/j.cyto.2023.156133

Cited by 4 publications

(2 citation statements)

References 45 publications

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“…Analyzing the supernatant of the PDTOs treated with the PI3K inhibitors for 48hs we observed that both patients shared a common alteration, the reduction of the amount of IL-8 released by tumor cells. IL-8 not only promotes NSCLC cells growth and survival but also interferes with T-cell function by inducing the upregulation of PDL-1 on tumor cells and inducing the apoptosis of subsets of effector CD8+ T-cells 55,56 . In addition to IL-8, IL-6 and MIF are the only cytokines detected that could be contributing to impairing Tcell functions in our system since they are capable of directly affecting T-cells effector function [57][58][59] .…”

Section: Discussionmentioning

confidence: 99%

Novel co-culture strategies of tumor organoids with autologous T-cells reveal clinically relevant combinations of immune-checkpoint and targeted therapies

Podaza

Capuano

Assaad

et al. 2023

Preprint

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Patient-derived tumor organoids (PDTOs) have become relevant pre-clinical models for therapeutic modeling since they highly recapitulate patients' responses to treatment. Nevertheless, their value for immunotherapy modeling has not been fully explored. We developed a tumor processing protocol that enables the establishment of PDTOs and tumor-infiltrating lymphocytes (TILs) isolation. By the optimization of functional assays, we compared the T-cells effector functions of matching PBMCs and TILs, demonstrating that PBMCs after co-culture and TILs after initial expansion display similar responses. In addition, the evaluation of cytokine production by fluorospot in combination with an image-based killing assay enables the screening of anti-PD-1 combinations with alternative immune checkpoint inhibitors as well as its combination with target inhibitors. Our proof-of-concept functional assays showed the potential and versatility of PDTOs and T-cell co-culture systems for immunotherapy screening. The optimization of scalable functional assays downstream co-culture represents a significant step forward to increase the value of PDTOs as pre-clinical models for immunotherapeutic screens.

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Section: Discussionmentioning

confidence: 99%

Novel co-culture strategies of tumor organoids with autologous T-cells reveal clinically relevant combinations of immune-checkpoint and targeted therapies

Podaza

Capuano

Assaad

et al. 2023

Preprint

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“…Here, at 2 months post-treatment, superior OS was seen in patients with a greater decrease in IL-8 compared with patients with an increase in IL-8 (median OS not reached at 20 months vs. 9.84 months, p = 0.025). In another study by Kang et al, in 44 patients with stage III-IV NSCLC, a decrease in plasma IL-8 three months following anti-PD-1 combined with hypo-fractionated radiotherapy was reported in patients with disease remission or stable disease, while patients with PD had increases in IL-8; lower levels of IL-8 after treatment were also associated with prolonged OS ( p = 0.0058) [ 42 ]. These studies collectively demonstrate that increases in IL-8 after ICI associate inversely with patient response.…”

Section: Circulating Levels Of Cytokines and Soluble Factorsmentioning

confidence: 99%

Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade

Tsai,

Schlom,

Donahue

2024

J Exp Clin Cancer Res

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The paradigm of non-small cell lung cancer (NSCLC) treatment has been profoundly influenced by the development of immune checkpoint inhibitors (ICI), but the range of clinical responses observed among patients poses significant challenges. To date, analyses of tumor biopsies are the only parameter used to guide prognosis to ICI therapy. Tumor biopsies, however, are often difficult to obtain and tissue-based biomarkers are limited by intratumoral heterogeneity and temporal variability. In response, there has been a growing emphasis on the development of “liquid biopsy”‒ derived biomarkers, which offer a minimally invasive means to dynamically monitor the immune status of NSCLC patients either before and/or during the course of treatment. Here we review studies in which multiple blood-based biomarkers encompassing circulating soluble analytes, immune cell subsets, circulating tumor DNA, blood-based tumor mutational burden, and circulating tumor cells have shown promising associations with the clinical response of NSCLC patients to ICI therapy. These investigations have unveiled compelling correlations between the peripheral immune status of patients both before and during ICI therapy and patient outcomes, which include response rates, progression-free survival, and overall survival. There is need for rigorous validation and standardization of these blood-based assays for broader clinical application. Integration of multiple blood-based biomarkers into comprehensive panels or algorithms also has the potential to enhance predictive accuracy. Further research aimed at longitudinal monitoring of circulating biomarkers is also crucial to comprehend immune dynamics and resistance mechanisms and should be used alongside tissue-based methods that interrogate the tumor microenvironment to guide treatment decisions and may inform on the development of novel therapeutic strategies. The data reviewed here reinforce the opportunity to refine patient stratification, optimize treatments, and improve outcomes not only in NSCLC but also in the wider spectrum of solid tumors undergoing immunotherapy.

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Conventional T Cell Subsets and Their Roles Within the Tumor Microenvironment

Azimnasab-Sorkhabi,

Soltani-Asl,

Ansa-Addo

et al. 2024

Interdisciplinary Cancer Research

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Interleukin 8 in plasma is an efficacy marker for advanced non-small cell lung cancer treated with hypofractionated radiotherapy and PD-1 blockade

Cited by 4 publications

References 45 publications

Novel co-culture strategies of tumor organoids with autologous T-cells reveal clinically relevant combinations of immune-checkpoint and targeted therapies

Novel co-culture strategies of tumor organoids with autologous T-cells reveal clinically relevant combinations of immune-checkpoint and targeted therapies

Blood-based biomarkers in patients with non-small cell lung cancer treated with immune checkpoint blockade

Conventional T Cell Subsets and Their Roles Within the Tumor Microenvironment

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