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Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial

Authors :
Gögenur, Mikail
Balsevicius, Lukas
Bulut, Mustafa
Colak, Nesibe
Justesen, Tobias Freyberg
Fiehn, Anne-Marie Kanstrup
Jensen, Marianne Bøgevang
Høst-Rasmussen, Kathrine
Cappelen, Britt
Gaggar, Shruti
Tajik, Asma
Zahid, Jawad Ahmad
Bennedsen, Astrid Louise Bjørn
D'Ondes, Tommaso Del Buono
Raskov, Hans
Sækmose, Susanne Gjørup
Hansen, Lasse Bremholm
Salanti, Ali
Brix, Susanne
Gögenur, Ismail
Gögenur, Mikail
Balsevicius, Lukas
Bulut, Mustafa
Colak, Nesibe
Justesen, Tobias Freyberg
Fiehn, Anne-Marie Kanstrup
Jensen, Marianne Bøgevang
Høst-Rasmussen, Kathrine
Cappelen, Britt
Gaggar, Shruti
Tajik, Asma
Zahid, Jawad Ahmad
Bennedsen, Astrid Louise Bjørn
D'Ondes, Tommaso Del Buono
Raskov, Hans
Sækmose, Susanne Gjørup
Hansen, Lasse Bremholm
Salanti, Ali
Brix, Susanne
Gögenur, Ismail
Source :
Gögenur , M , Balsevicius , L , Bulut , M , Colak , N , Justesen , T F , Fiehn , A-M K , Jensen , M B , Høst-Rasmussen , K , Cappelen , B , Gaggar , S , Tajik , A , Zahid , J A , Bennedsen , A L B , D'Ondes , T D B , Raskov , H , Sækmose , S G , Hansen , L B , Salanti , A , Brix , S & Gögenur , I 2023 , ' Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial ' , Journal for ImmunoTherapy of Cancer , vol. 11 , no. 5 , e006774 .
Publication Year :
2023

Abstract

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05).Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infil

Details

Database :
OAIster
Journal :
Gögenur , M , Balsevicius , L , Bulut , M , Colak , N , Justesen , T F , Fiehn , A-M K , Jensen , M B , Høst-Rasmussen , K , Cappelen , B , Gaggar , S , Tajik , A , Zahid , J A , Bennedsen , A L B , D'Ondes , T D B , Raskov , H , Sækmose , S G , Hansen , L B , Salanti , A , Brix , S & Gögenur , I 2023 , ' Neoadjuvant intratumoral influenza vaccine treatment in patients with proficient mismatch repair colorectal cancer leads to increased tumor infiltration of CD8+ T cells and upregulation of PD-L1: a phase 1/2 clinical trial ' , Journal for ImmunoTherapy of Cancer , vol. 11 , no. 5 , e006774 .
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1397135747
Document Type :
Electronic Resource