Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: an analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study.

Amrein, M. A.; Bührer, E. D.; Amrein, M. L.; Li, Q.; Rothschild, S.; Riether, C.; Jaggi, R.; Savic-Prince, S.; Bubendorf, L.; Gautschi, O.; Ochsenbein, A. (2021). Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: an analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study. Cancer immunology, immunotherapy : CII, 70(2), pp. 405-415. Springer 10.1007/s00262-020-02688-4

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BACKGROUND

Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second-line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first-line treatment of NSCLC. However, the effect of conventional first-line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown.

METHODS

We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated.

RESULTS

We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy.

CONCLUSION

Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Amrein, Michael Alex; Bührer, Elias; Amrein, Martin Lukas; Riether, Carsten and Ochsenbein, Adrian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1432-0851

Publisher:

Springer

Language:

English

Submitter:

Rebeka Gerber

Date Deposited:

26 Aug 2020 14:46

Last Modified:

31 Mar 2021 18:47

Publisher DOI:

10.1007/s00262-020-02688-4

PubMed ID:

32767058

Uncontrolled Keywords:

Chemotherapy Immune checkpoint Immune microenvironment Non-small-cell lung cancer

BORIS DOI:

10.7892/boris.146104

URI:

https://boris.unibe.ch/id/eprint/146104

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