E D Bührer1,2,3, M A Amrein1,2,3, M L Amrein1, Q Li4, S Rothschild5, C Riether1,3, R Jaggi1, S Savic-Prince6, L Bubendorf6, O Gautschi7, A F Ochsenbein8,9. 1. Department for BioMedical Research, University of Bern, Bern, Switzerland. 2. Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. 3. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 4. Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland. 5. Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. 6. Institute of Pathology, University Hospital Basel, Basel, Switzerland. 7. Department of Medical Oncology, Cantonal Hospital Lucerne, Lucerne, Switzerland. 8. Department for BioMedical Research, University of Bern, Bern, Switzerland. adrian.ochsenbein@insel.ch. 9. Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. adrian.ochsenbein@insel.ch.
Abstract
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.
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.
Entities:
Keywords:
Chemotherapy; Immune checkpoint; Immune microenvironment; Non-small-cell lung cancer
Authors: Shuting Han; Joshua K Tay; Celestine Jia Ling Loh; Axel Jun Ming Chu; Joe Poh Sheng Yeong; Chwee Ming Lim; Han Chong Toh Journal: Front Immunol Date: 2021-12-10 Impact factor: 7.561