The Tumor Immune Microenvironment Is Associated With Recurrence in Early-Stage Lung Adenocarcinoma

肿瘤免疫微环境与早期肺腺癌复发相关

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作者:Hiroaki Kanemura, Toshihide Yokoyama, Ryu Nakajima, Atsushi Nakamura, Hiroaki Kuroda, Yoshitaka Kitamura, Hiroyasu Shoda, Nobuaki Mamesaya, Yoshihiro Miyata, Tatsuro Okamoto, Kyoichi Okishio, Masahide Oki, Yuichi Sakairi, Toyofumi Fengshi Chen-Yoshikawa, Tadashi Aoki, Tatsuo Ohira, Isao Matsumoto, K

Conclusions

PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

Methods

This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD-L1) expression on tumor cells, CD8 expression on tumor-infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD-L1 tumor proportion score and CD8+ tumor-infiltrating lymphocyte density. The association between each potential biomarker and relapse-free survival (RFS) during adjuvant chemotherapy was assessed by Kaplan-Meier analysis.

Results

A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo-not reached; n = 39) and 23.7 months (95% CI: 14.5-43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log-rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29-0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD-L1 expression on tumor cells, CD8+ T cell infiltration, and TP53 mutation status may help identify patients with early-stage NSCLC susceptible to recurrence after adjuvant chemotherapy.

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