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Predictive and Prognostic Implications of Circulating CX3CR1(+) CD8(+) T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy

Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti–programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8(+) T cells expres...

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Detalles Bibliográficos
Autores principales: Abdelfatah, Eihab, Long, Mark D., Kajihara, Ryutaro, Oba, Takaaki, Yamauchi, Takayoshi, Chen, Hongbin, Sarkar, Joy, Attwood, Kristopher, Matsuzaki, Junko, Segal, Brahm H., Dy, Grace K., Ito, Fumito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10060186/
https://www.ncbi.nlm.nih.gov/pubmed/37009132
http://dx.doi.org/10.1158/2767-9764.CRC-22-0383
Descripción
Sumario:Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti–programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8(+) T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti–PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1(+)CD8(+) T cells as a predictive correlate of response to chemo-immunotherapy in patients with non–small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1(+) subset in circulating CD8(+) T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan–Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires. SIGNIFICANCE: Current approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.