Therapeutic advances in medical oncology · 2026
CD39+CD8+ T cell infiltration is associated with clinical outcomes of subsequent immunotherapy in advanced EGFR-mutant non-small cell lung cancer.
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Lu Wanjun, Wu Qiuxia, Wang Zimu, Cheng Qinpei, Zuo Xueying, Liu Xin, Lv Jiawen, Song Yong, Zhang Fang, Lv Tangfeng
Аннотация
BACKGROUND: Immunotherapy has demonstrated limited efficacy in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), often due to an immunosuppressive tumor microenvironment (TME). The clinical significance of the CD39-adenosine pathway in this refractory setting remains unclear.
OBJECTIVE: To explore the role of the CD39-adenosine pathway, especially CD39, in EGFR-mutant (EGFR-Mu) NSCLC patients who received immunotherapy as a second or later-line treatment.
DESIGN: In this retrospective study, clinical characteristics, treatment regimens, and efficacy endpoints (progression-free survival (PFS) and objective response rate (ORR)) were collected. We analyzed the correlation between CD39 expression, CD39+CD8+ T cell infiltration, and clinical outcomes.
METHODS: We retrospectively evaluated EGFR-Mu NSCLC patients receiving later-line immune checkpoint inhibitors (ICIs) at Jinling Hospital, alongside The Cancer Genome Altas (TCGA) cohort data. TME phenotyping (CD39, CD73, ADORA1, and CD39+CD8+/PD-1+CD8+ T cell infiltration) was performed using immunohistochemistry and immunofluorescence. Patients were divided into a response group and a non-response group according to the Tumor Efficacy Assessment Criteria (RECIST 1.1). Univariate and multivariate Cox regression analyses were used to explore the factors influencing the survival of EGFR-Mu patients who received ICIs in the second line or later lines.
RESULTS: Database and clinical samples analyses revealed that expression of CD39 and CD73 was significantly increased in EGFR-Mu NSCLC samples compared to EGFR wild-type (EGFR-WT). However, Immunofluorescence (IF) results showed that the infiltration rate of CD39+CD8+ T cells was significantly lower in EGFR-Mu patients than in EGFR-WT patients. Notably, low overall CD39 expression and high CD39+CD8+ T cell infiltration within the TME were correlated with favorable immunotherapy responses. Among the 19 EGFR-Mu patients receiving ICIs, the overall ORR was 10.5%, and the median PFS for EGFR-Mu patients was 4.53 months. Multivariate Cox regression analysis found brain metastasis as an independent risk factor, while the infiltration of CD39+CD8+ T cells and PD-1+CD8+ T cells independently correlated with prolonged PFS.
CONCLUSION: Our exploratory findings suggest that CD39+CD8+ T cell infiltration may serve as a putative biomarker associated with immunotherapy response in EGFR-mutant NSCLC. Evaluating the CD39-adenosine pathway within the TME could inform future personalized treatment strategies, warranting further validation in larger, prospective cohorts.
OBJECTIVE: To explore the role of the CD39-adenosine pathway, especially CD39, in EGFR-mutant (EGFR-Mu) NSCLC patients who received immunotherapy as a second or later-line treatment.
DESIGN: In this retrospective study, clinical characteristics, treatment regimens, and efficacy endpoints (progression-free survival (PFS) and objective response rate (ORR)) were collected. We analyzed the correlation between CD39 expression, CD39+CD8+ T cell infiltration, and clinical outcomes.
METHODS: We retrospectively evaluated EGFR-Mu NSCLC patients receiving later-line immune checkpoint inhibitors (ICIs) at Jinling Hospital, alongside The Cancer Genome Altas (TCGA) cohort data. TME phenotyping (CD39, CD73, ADORA1, and CD39+CD8+/PD-1+CD8+ T cell infiltration) was performed using immunohistochemistry and immunofluorescence. Patients were divided into a response group and a non-response group according to the Tumor Efficacy Assessment Criteria (RECIST 1.1). Univariate and multivariate Cox regression analyses were used to explore the factors influencing the survival of EGFR-Mu patients who received ICIs in the second line or later lines.
RESULTS: Database and clinical samples analyses revealed that expression of CD39 and CD73 was significantly increased in EGFR-Mu NSCLC samples compared to EGFR wild-type (EGFR-WT). However, Immunofluorescence (IF) results showed that the infiltration rate of CD39+CD8+ T cells was significantly lower in EGFR-Mu patients than in EGFR-WT patients. Notably, low overall CD39 expression and high CD39+CD8+ T cell infiltration within the TME were correlated with favorable immunotherapy responses. Among the 19 EGFR-Mu patients receiving ICIs, the overall ORR was 10.5%, and the median PFS for EGFR-Mu patients was 4.53 months. Multivariate Cox regression analysis found brain metastasis as an independent risk factor, while the infiltration of CD39+CD8+ T cells and PD-1+CD8+ T cells independently correlated with prolonged PFS.
CONCLUSION: Our exploratory findings suggest that CD39+CD8+ T cell infiltration may serve as a putative biomarker associated with immunotherapy response in EGFR-mutant NSCLC. Evaluating the CD39-adenosine pathway within the TME could inform future personalized treatment strategies, warranting further validation in larger, prospective cohorts.