172 Cancer immunotherapy response monitoring with whole blood immuno-transcriptomic profiling

转录组 免疫疗法 肿瘤科 黑色素瘤 癌症 免疫检查点 基因表达谱 内科学 癌症免疫疗法 佐剂 医学 免疫系统 癌症研究 基因表达 基因 生物 免疫学 生物化学
作者
Pedro Romero,Laura Ciarloni,Noushin Hadadi,Rutger H.T. Koornstra,Sandra van Wilpe,Eric Durandau,Sahar Hosseinian Ehrensberger,Sylvain Monnier-Benoit,Niven Mehra
标识
DOI:10.1136/jitc-2023-sitc2023.0172
摘要

Background

Immune checkpoint inhibitor (ICI)-based immunotherapy has become standard of care in a growing number of advanced cancer indications. Recently, its use has been extended to the adjuvant and even neoadjuvant settings in a few solid tumor types. Despite this tremendous progress, however, a significant proportion of patients across cancer types fail to achieve clinical benefit. For metastatic melanoma (MM), the response rate is 40–60%. Redirecting non-responding patients to other therapeutic options is desired to avoid unnecessary side effects and improve patient outcomes. Whole blood transcriptome has been successfully applied to ICI response monitoring in metastatic urothelial cancer1 and shows great potential for MM.

Methods

Whole blood samples from 29 patients with BRAF+ and high lactate dehydrogenase MM were collected before and after 6 or 12 weeks of anti-PD-1/CTLA-4 combination treatment. Nineteen were classified as responders (R) (progression-free survival (PFS) ≥ 6 months) and 10 as non-responders (NR).Transcriptome profiles were generated by RNA-seq and Differential Expression Genes (DEG) were identified by combining differential expression analysis (DEA) and advanced multivariate machine learning analysis (MLA). Biological relevancy was assessed by over representation and gene network analysis.

Results

DEA and MLA between baseline and on-treatment samples from responders (R) identified 141 DEGs associated with early response to the treatment. Functional analysis of the 141 DEGs revealed upregulated cell proliferation, immune checkpoint proteins and interferon-regulated genes. These results are in line with theoretical expectations from the therapy. Interestingly, similar pathway enrichments were observed in our previous analysis of a mUC ICI-treated cohort,1 suggesting a common modulation of immune programming upon immunotherapy, independent of the targeted disease.

Conclusions

In conclusion, whole blood immuno-transcriptome profiling combined with proprietary advanced data analytics identified biomarkers for the monitoring of ICI response in MM and mUC and offers new insights that may help understanding the underlying processes and mechanism of action.

Reference

vanWilpe S, Wosika V, Ciarloni L. Whole Blood Transcriptome Profiling Identifies DNA Replication and Cell Cycle Regulation as Early Marker of Response to Anti-PD-1 in Patients with Urothelial Cancer. Cancers. 2021;13.
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