Gene Expressions and High Lymphocyte Count May Predict Durable Clinical Benefits in Patients with Advanced Non-Small-Cell Lung Cancer Treated with Immune Checkpoint Inhibitors

Author:

Mouritzen Mette T.123ORCID,Ladekarl Morten123ORCID,Hager Henrik45,Mattesen Trine B.4ORCID,Lippert Julie B.4,Frank Malene S.67ORCID,Nøhr Anne K.28,Egendal Ida B.28ORCID,Carus Andreas123

Affiliation:

1. Department of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9000 Aalborg, Denmark

2. Clinical Cancer Research Centre, Aalborg University Hospital, Sdr. Skovvej 15, 9000 Aalborg, Denmark

3. Department of Clinical Medicine, Aalborg University, Selma Lagerløfs Vej 249, 9260 Gistrup, Denmark

4. Department of Clinical Pathology, Vejle Hospital, University Hospital of Southern Denmark, Beriderbakken 4, 7100 Vejle, Denmark

5. Department of Clinical Research, University of Southern Denmark, J.B. Winsløws Vej 19.3, 5000 Odense, Denmark

6. Department of Clinical Oncology and Palliative Care, Zealand University Hospital, Sygehusvej 10, 4000 Roskilde, Denmark

7. Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark

8. Center for Clinical Data Science (CLINDA), Aalborg University and Aalborg University Hospital, Sdr. Skovvej 15, 9000 Aalborg, Denmark

Abstract

Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n = 25), GEP was performed using the nCounter® PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, p = 0.038 and OR = 0.36, p = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted p-values < 0.05). Conclusions: ALC above 1.01 × 109/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.

Funder

Danish Health Authority’s ‘Cancer Immunotherapy Research Grant

Medical Fund of the Danish Regions

NEYE fonden

Minister Erna Hamiltons Legat for Videnskab og Kunst

Grosserer M. Brogaard og Hustrus Mindefond

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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