Pembrolizumab has been approved as first‐line treatment for advanced Non‐small cell lung cancer (NSCLC) patients with tumors expressing PD‐L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty‐six consecutive advanced NSCLC patients treated with pembrolizumab in first‐line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD‐L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B‐cells, CD45, T‐cells, CD8 T‐cells and NK cells. Immune cell scores such as CD8 T‐cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD‐ L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.

Biomarkers and gene signatures to predict durable response to pembrolizumab in non‐small cell lung cancer

Poma A. M.;Bruno Rossella.;Pietrini I.;Proietti A.;Vasile E.;Cappelli S.;Chella A.;Fontanini Gabriella
2021-01-01

Abstract

Pembrolizumab has been approved as first‐line treatment for advanced Non‐small cell lung cancer (NSCLC) patients with tumors expressing PD‐L1 and in the absence of other targetable alterations. However, not all patients that meet these criteria have a durable benefit. In this monocentric study, we aimed at refining the selection of patients based on the expression of immune genes. Forty‐six consecutive advanced NSCLC patients treated with pembrolizumab in first‐line setting were enrolled. The expression levels of 770 genes involved in the regulation of the immune system was analysed by the nanoString system. PD‐L1 expression was evaluated by immunohistochemistry. Patients with durable clinical benefit had a greater infiltration of cytotoxic cells, exhausted CD8, B‐cells, CD45, T‐cells, CD8 T‐cells and NK cells. Immune cell scores such as CD8 T‐cell and NK cell were good predictors of durable response with an AUC of 0.82. Among the immune cell markers, XCL1/2 showed the better performance in predicting durable benefit to pembrolizumab, with an AUC of 0.85. Additionally, CD8A, CD8B and EOMES showed a high specificity (>0.86) in identifying patients with a good response to treatment. In the same series, PD‐ L1 expression levels had an AUC of 0.61. The characterization of tumor microenvironment, even with the use of single markers, can improve patients’ selection for pembrolizumab treatment.
2021
Poma, A. M.; Bruno, Rossella.; Pietrini, I.; Ali, G.; Pasquini, G.; Proietti, A.; Vasile, E.; Cappelli, S.; Chella, A.; Fontanini, Gabriella
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1113722
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