Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

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MARC

Eltahir, MohamedUppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi (author)

Plasma Proteomic Analysis in Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Blockade

Article/chapterEnglish2021

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2021-06-22
MDPI,2021
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-453032
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-453032URI
https://doi.org/10.3390/cancers13133116DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:147001506URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Simple Summary Immunotherapy leads to highly variable responses in lung cancer patients. We assessed the value of a blood-based test to predict which patients would benefit from this new treatment modality. We determined that some patients have higher and lower levels of immune markers in their blood samples, and that this is related to better survival without tumor growth. The blood test has the potential to help select the optimal therapy for lung cancer patients. Checkpoint inhibitors have been approved for the treatment of non-small cell lung cancer (NSCLC). However, only a minority of patients demonstrate a durable clinical response. PD-L1 scoring is currently the only biomarker measure routinely used to select patients for immunotherapy, but its predictive accuracy is modest. The aim of our study was to evaluate a proteomic assay for the analysis of patient plasma in the context of immunotherapy. Pretreatment plasma samples from 43 NSCLC patients who received anti-PD-(L)1 therapy were analyzed using a proximity extension assay (PEA) to quantify 92 different immune oncology-related proteins. The plasma protein levels were associated with clinical and histopathological parameters, as well as therapy response and survival. Unsupervised hierarchical cluster analysis revealed two patient groups with distinct protein profiles associated with high and low immune protein levels, designated as "hot" and "cold". Further supervised cluster analysis based on T-cell activation markers showed that higher levels of T-cell activation markers were associated with longer progression-free survival (PFS) (p < 0.01). The analysis of single proteins revealed that high plasma levels of CXCL9 and CXCL10 and low ADA levels were associated with better response and prolonged PFS (p < 0.05). Moreover, in an explorative response prediction model, the combination of protein markers (CXCL9, CXCL10, IL-15, CASP8, and ADA) resulted in higher accuracy in predicting response than tumor PD-L1 expression or each protein assayed individually. Our findings demonstrate a proof of concept for the use of multiplex plasma protein levels as a tool for anti-PD-(L)1 response prediction in NSCLC. Additionally, we identified protein signatures that could predict the response to anti-PD-(L)1 therapy.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Cancer och onkologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cancer and Oncology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Klinisk laboratoriemedicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Clinical Laboratory Medicine hsv//eng
lung cancer
biomarkers
liquid biopsy
immune checkpoint inhibitors
PD-L1
Pathology
Patologi

Added entries (persons, corporate bodies, meetings, titles ...)

Isaksson, JohanUppsala universitet,Klinisk och experimentell patologi,Centrum för klinisk forskning, Gävleborg(Swepub:uu)johis237 (author)
Mattsson, Johanna Sofia Margareta,1985-Uppsala universitet,Klinisk och experimentell patologi,Patrick Micke(Swepub:uu)johma961 (author)
Karre, KlasKarolinska Inst, Dept Microbiol Cell & Tumor Biol, S-17177 Stockholm, Sweden. (author)
Botling, JohanUppsala universitet,Klinisk och experimentell patologi,Johan Botling(Swepub:uu)johanbot (author)
Lord, MartinUppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab(Swepub:uu)marlo206 (author)
Mangsbo, Sara,1981-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap(Swepub:uu)saman132 (author)
Micke, PatrickUppsala universitet,Klinisk och experimentell patologi,Patrick Micke(Swepub:uu)patmi676 (author)
Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

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In:Cancers: MDPI13:132072-6694

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Clinical Laborat ...

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