ArticleBiomarker research2026
Plasmatic CXCL13 as a biomarker of primary resistance to immunotherapy and impaired peripheral immunity in non-small cell lung cancer.
Article in Biomarker research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03838159 (A Randomized Phase II Study of Neo-adjuvant Chemo/Immunotherapy Versus Chemotherapy Alone for the Treatment of Locally Advanced and Potentially Resectable Non-small Cell Lung Cancer), which is not on this map. Not yet cited in PubMed.
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A Randomized Phase II Study of Neo-adjuvant Chemo/Immunotherapy Versus Chemotherapy Alone for the Treatment of Locally Advanced and Potentially Resectable Non-small Cell Lung Cancer (NSCLC) Patients.
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Abstract
backgroundImmunotherapy (IO) has improved prognosis of non-small cell lung cancer (NSCLC); however, some patients experience primary IO resistance (PIR). CXCL13 could be a promising PIR biomarker due to its role in antitumor immune responses.
methods177 patients with stage IV NSCLC receiving IO from the observational, multicenter, real-world study BLI-O were included from 15 centers in Spain. CXCL13 and 39 other cytokines were measured in 158 baseline (BS1) and 98 post-first-cycle of IO (BS2) plasma samples. Additionally, peripheral T and B cell BS2 immunophenotypes were determined. CXCL13 levels were also measured in plasma samples from 38 stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy from the NADIM II trial (NCT03838159). PIR was defined as disease progression within 3 months in non-surgical cases or incomplete pathological response in surgical cases.
resultsMetastatic PIR patients had higher CXCL13 plasma levels compared to non-PIR patients, especially in BS2 samples, and exhibited a greater increase of CXCL13 levels after the first cycle of IO. Patients with high BS2 CXCL13 levels showed shorter PFS (p = 0.0002) and OS (p = 0.0007). Females showed a lower percentage of high CXCL13 cases compared to male cases. CXCL13 did not influence the growth of NSCLC cell lines in vitro. Moreover, the expression of the CXCL13/CXCR5 axis was restricted to the immune compartment of tumors. Plasmatic CXCL13 levels were not associated with PD-L1 TPS expression nor TLS density in tumor tissue. However, at systemic level, patients with high CXCL13 levels exhibited impaired B and T cell phenotypes, along with elevated levels of inflammatory cytokines, after first IO cycle. Finally, high BS2 CXCL13 levels in resectable cases were also associated with PIR.
conclusionsElevated CXCL13 levels after the first cycle of IO are associated with PIR and an altered peripheral immune profile in NSCLC, supporting its potential as a prognostic biomarker in these patients.
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