The effect of neoadjuvant therapy on PD-L1 expression and CD8+lymphocyte density in non-small cell lung cancer.

Zens, Philipp; Bello, Corina Manuela; Scherz, Amina; von Gunten, Michael; Ochsenbein, Adrian; Schmid, Ralph A; Berezowska, Sabina (2022). The effect of neoadjuvant therapy on PD-L1 expression and CD8+lymphocyte density in non-small cell lung cancer. Modern pathology, 35(12), pp. 1848-1859. Springer Nature 10.1038/s41379-022-01139-y

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PD-L1 expression is the routine clinical biomarker for the selection of patients to receive immunotherapy in non-small cell lung cancer (NSCLC). However, the application and best timing of immunotherapy in the resectable setting is still under investigation. We aimed to study the effect of chemotherapy on PD-L1 expression and tumor infiltrating lymphocytes (TILs), which is to date still poorly understood. Our retrospective, single-centre neoadjuvant cohort comprised 96 consecutive patients with NSCLC resected 2000-2016 after neoadjuvant therapy, including paired diagnostic chemo-naïve specimens in 53 cases. A biologically matched surgical cohort of 114 primary resected cases was included. PD-L1 expression, CD8 + TILs density and tertiary lymphoid structures were assessed on whole slides and correlated with clinico-pathological characteristics and survival. Seven/53 and 12/53 cases had lower respectively higher PD-L1 expressions after neoadjuvant therapy. Most cases (n = 34) showed no changes in PD-L1 expression, the majority of these harboring PD-L1 < 1% in both samples (21/34 [61.8%]). Although CD8 + TILs density was significantly higher after chemotherapy (p = 0.031) in resections compared to diagnostic biopsies, this might be due to sampling and statistical bias. No difference in PD-L1 expression or CD8 + TILs density was detected when comparing the neoadjuvant and surgical cohort. In univariable analyses, higher CD8 + TILs density, higher numbers of tertiary lymphoid structures but not PD-L1 expression were significantly associated with longer survival. Increased PD-L1 expression after neoadjuvant chemotherapy was not significantly associated with shorter 5-year survival, but the number of cases was very low. In multivariable analysis, only pT category and age remained independent prognostic factors. In summary, PD-L1 expression was mostly unchanged after neoadjuvant chemotherapy compared to diagnostic biopsies. The sample size of cases with changed PD-L1 expression was too small to draw conclusions on any prognostic value.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Zens, Philipp Immanuel, Bello, Corina Manuela, Scherz, Amina, Ochsenbein, Adrian, Schmid, Ralph, Berezowska, Sabina Anna


600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology




Springer Nature




Pubmed Import

Date Deposited:

03 Aug 2022 11:20

Last Modified:

05 Dec 2022 16:22

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