CXCL13 Positive Cells Localization Predict Response to Anti-PD-1/PD-L1 in Pulmonary Non-Small Cell Carcinoma
Fatemeh Vahidian1,2, Fabien C Lamaze1, Cédrik Bouffard1,2
1Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Quebec City, QC G1V 4G5, Canada.
Cancers
|February 24, 2024
Summary
CXCL13+ T cells predict immune checkpoint inhibitor response in non-small cell lung cancer (NSCLC). Their location in tertiary lymphoid structures (TLS) indicates a favorable prognosis, while elsewhere suggests a poor prognosis.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune checkpoint inhibitors (ICIs) offer revolutionary treatment for non-small cell lung cancer (NSCLC), yet response rates remain limited to 20-30%.
- PD-L1 expression is the sole approved biomarker for ICI response in NSCLC, but its predictive value is suboptimal.
- CXCL13+ T cells within the tumor microenvironment (TME) are emerging as potential predictors of ICI efficacy.
Purpose of the Study:
- To investigate the predictive value of CXCL13+ cell localization within the tumor microenvironment (TME) for immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC).
Main Methods:
- Retrospective analysis of 65 advanced NSCLC patients treated with Nivolumab/Pembrolizumab.
- Immunohistochemistry (IHC) for CXCL13 on tumor specimens to quantify cell density in tumor, invasive margin, non-tumor, and tertiary lymphoid structure (TLS) compartments.
- Cox models and Mann-Whitney tests were used to correlate CXCL13+ cell density with progression-free survival (PFS) and overall survival (OS).
Main Results:
- Increased CXCL13+ cell density in most TME compartments correlated with poorer overall survival (OS) and progression-free survival (PFS).
- Conversely, higher CXCL13+ cell density specifically within tertiary lymphoid structures (TLS) was associated with improved PFS.
- These findings highlight the differential prognostic impact of CXCL13+ cell localization within the tumor microenvironment.
Conclusions:
- CXCL13+ cell localization within the tumor microenvironment (TME) is a significant predictor of immune checkpoint inhibitor (ICI) efficacy in advanced non-small cell lung cancer (NSCLC).
- Favorable prognosis is linked to CXCL13+ cells within tertiary lymphoid structures (TLS), potentially enhancing antigen presentation.
- Unfavorable prognosis is associated with CXCL13+ cells in other TME compartments, suggesting distinct roles and warranting further clinical validation.
Keywords:
CXCL13Non-small cell lung cancers (NSCLCs)immune checkpoint inhibitor treatments (ICIs)tertiary lymphoid structure (TLS)tumor microenvironment (TME)
