Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy
| Autor: | Anna Larissa N. Niemeijer, Sara Sahba, Adrianus J. de Langen, Egbert F. Smit, Birgit I. Lissenberg-Witte, Erik Thunnissen |
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| Přispěvatelé: | Pulmonary medicine, CCA - Cancer biology and immunology, AII - Cancer immunology, Epidemiology and Data Science, Pathology, APH - Methodology |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Stromal cell CD3 Complex CD8 Antigens medicine.medical_treatment Programmed Cell Death 1 Receptor B7-H1 Antigen Article Prognostic markers 03 medical and health sciences Antineoplastic Agents Immunological 0302 clinical medicine Carcinoma Non-Small-Cell Lung Internal medicine PD-L1 Tumor Microenvironment medicine Carcinoma Humans Lung cancer Survival analysis Aged Retrospective Studies 030304 developmental biology 0303 health sciences Chemotherapy biology business.industry Immunotherapy Middle Aged medicine.disease Survival Analysis Gene Expression Regulation Neoplastic Nivolumab Treatment Outcome 030220 oncology & carcinogenesis CD4 Antigens biology.protein Female business Non-small-cell lung cancer |
| Zdroj: | British Journal of Cancer, 123(3), 392-402. SPRINGERNATURE Niemeijer, A L N, Sahba, S, Smit, E F, Lissenberg-Witte, B I, de Langen, A J & Thunnissen, E 2020, ' Association of tumour and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with DCB and OS to nivolumab treatment in NSCLC patients pre-treated with chemotherapy ', British Journal of Cancer, vol. 123, no. 3, pp. 392-402 . https://doi.org/10.1038/s41416-020-0888-5 British Journal of Cancer, 123(3), 392-402. Nature Publishing Group British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Background Immune checkpoint inhibitors are most beneficial in patients with high tumour PD-L1 expression. However, the use of PD-L1 expression is not straightforward. We investigated PD-L1 expression and immune cell (IC) infiltrates in non-small-cell lung cancer (NSCLC) patients treated with nivolumab. Methods Tumour tissue specimens of 139 NSCLC patients were scored for tumour/stromal PD-L1 and various IC expression markers, and associated with durable clinical benefit (DCB) and overall survival (OS). Results Median OS was higher for patients with high stromal infiltration of CD8+ ICs (9.0 months) compared with patients with low and intermediate infiltration (both 5.0 months, p = 0.035) and for patients with high infiltration of stromal CD4+ ICs (9.0 months) compared with patients with low and intermediate infiltration (both 5.0 months, p = 0.010) and this was confirmed in the validation cohort. Post hoc analyses showed that biopsies taken after the last line of chemotherapy (ACT) were predictive for DCB and OS, whereas samples obtained before the last line of chemotherapy (BCT) were not. Conclusions Stromal infiltration of ICs can predict response to PD-1-directed immunotherapy in NSCLC patients. Interestingly, we found differences in the predictive value of IC markers between the ACT and BCT biopsies, suggesting that chemotherapy might influence the immune microenvironment. |
| Databáze: | OpenAIRE |
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