High farnesoid X receptor expression predicts favorable clinical outcomes in PDL1low/negative nonsmall cell lung cancer patients receiving antiPD1based chemoimmunotherapy.
Int J Oncol
; 60(4)2022 04.
Article
de En
| MEDLINE
| ID: mdl-35211760
ABSTRACT
Antiprogrammed death1 (PD1)/programmed deathligand 1 (PDL1)directed immunotherapy has revolutionized the treatment of advanced nonsmall cell lung cancer (NSCLC). However, predictive biomarkers are still lacking, particularly in identifying PDL1low/negative patients who will benefit from immunotherapy. It was previously reported that farnesoid X receptor (FXR) downregulated PDL1 expression in NSCLC, and that FXRhighPDL1low mouse Lewis lung carcinoma tumors showed an increased susceptibility to PD1 blockade compared with mock tumors. At present, whether the FXRhighPDL1low phenotype predicts clinical response to immunotherapy in patients with NSCLC remains unclear. Herein, a retrospective study was conducted to examine the expression levels of FXR, PDL1 and CD8+ T cells by immunohistochemistry in a cohort of 149 patients with NSCLC receiving antiPD1based chemoimmunotherapy. The results revealed that high FXR and PDL1 expression levels were associated with higher objective response rates (ORR) in all patients. High PDL1 expression also indicated superior progressionfree survival (PFS). Interestingly, an inverse correlation was identified between FXR and PDL1 expression in specimens with NSCLC. Subgroup analysis revealed that high FXR expression was associated with a higher ORR, as well as longer PFS and overall survival (OS) in PDL1low patients. Cox multivariate analysis revealed that high FXR expression was an independent predictor for PFS and OS in PDL1low patients. Tumor microenvironment evaluation revealed a statistically significant decrease of infiltrating CD8+ T cells in FXRhigh specimens with NSCLC. Overall, the present study proposed an FXRhighPDL1low signature as a candidate predictor of response to antiPD1based chemoimmunotherapy in PDL1low/negative patients with NSCLC, providing evidence that could be used to broaden the patients benefitting from immunotherapy.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Valeur prédictive des tests
/
Récepteurs cytoplasmiques et nucléaires
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Carcinome pulmonaire non à petites cellules
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Antigène CD274
Type d'étude:
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limites:
Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Langue:
En
Journal:
Int J Oncol
Sujet du journal:
NEOPLASIAS
Année:
2022
Type de document:
Article