Chemoradiotherapy efficacy is predicted by intra-tumour CD8+/FoxP3+ double positive T cell density in locally advanced N2 non-small-cell lung carcinoma.

Radiotherapy is a standard of care for locally advanced stage III N2 non-small-cell lung carcinoma (NSCLC) combined with surgery/chemotherapy. Radiotherapy is hypothesised to induce tumour immunogenic cell death, to release neoantigen resulting in intra-tumoural immune infiltration and abscopal effect. Conversely, it has not been demonstrated if immune cells are necessary to drive radiotherapy efficacy and predict patient's survival. We retrospectively analysed tumour samples and clinical data from 113 patients, 89 resected (PORT) and 24 non-resected (DRC) N2-NSCLC treated with chemotherapy and radiotherapy (same radiotherapy department from 2002 to 2015). The immune environment was characterised with in situ multiplex staining (CD8, FoxP3, PD-L1 and cytokeratin) and correlated with clinical data and survival. High density of CD8+ T cells was associated with OS (p = 0.04, HR = 1.93 [0.99-3.78]) and DFS (p = 0.003, HR = 2.42 [1.31-4.47]) in the PORT. High density of CD8+/FoxP3+ double positive cells was associated with OS (p = 0.01, HR = 1.97 [1.11-3.48]) in the whole population, with OS (p = 0.05, HR = 1.92 [0.98-3.74]) and PFS (p = 0.03, HR = 1.83 [1.03-3.23]) in the PORT without reaching significance for the DRC. Intermediate PD-L1 expression in tumour cells (TPS = 1-49%) was associated with a higher survival in the PORT. Intra-tumoural CD8+ T cell and particularly CD8+/FoxP3+ double positive T cell densities predict survival in stage III N2-NSCLC suggesting the need for a pre-existing intra-tumour immunity to mediate the action of radiotherapy. Density of CD8+/FoxP3+ cells was the best predictor of patient's survival in multivariate analysis and could represent a biomarker of radiotherapy efficacy.

Boulle G ，Velut Y ，Mansuet-Lupo A ，Gibault L ，Blons H ，Fournel L ，Boni A ，Cremer I ，Wislez M ，Duchatelle V ，Trédaniel J ，Hammond SA ，Herbst R ，Alifano M ，Giraud P ，Damotte D ... -  《-》

Expressions of CD8+TILs, PD-L1 and Foxp3+TILs in stage I NSCLC guiding adjuvant chemotherapy decisions.

Teng F ，Meng X ，Wang X ，Yuan J ，Liu S ，Mu D ，Zhu H ，Kong L ，Yu J ... -  《Oncotarget》

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer.

Yoneda K ，Kuwata T ，Kanayama M ，Mori M ，Kawanami T ，Yatera K ，Ohguri T ，Hisaoka M ，Nakayama T ，Tanaka F ... -  《-》

Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

Gennen K ，Käsmann L ，Taugner J ，Eze C ，Karin M ，Roengvoraphoj O ，Neumann J ，Tufman A ，Orth M ，Reu S ，Belka C ，Manapov F ... -  《Radiation Oncology》

Predictive relevance of PD-L1 expression combined with CD8+ TIL density in stage III non-small cell lung cancer patients receiving concurrent chemoradiotherapy.

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but little is known about factors predictive of efficacy in patients with locally advanced non-small cell lung cancer (NSCLC). We investigated the predictive relevance of PD-L1 expression and CD8+ tumour-infiltrating lymphocytes (TILs) density in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 74 consecutive patients with stage III NSCLC who had received CCRT. PD-L1 expression and CD8+ TIL density were evaluated by immunohistochemical analysis. Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression-free survival (PFS) and OS, whereas PD-L1 expression was not correlated with PFS and OS. Sub-analysis revealed that the PD-L1+/CD8 low group had the shortest PFS (8.6 months, p = 0.02) and OS (13.9 months, p = 0.11), and that the PD-L1-/CD8 high group had the longest prognosis (median PFS and OS were not reached) by Kaplan-Meier curves of the four sub-groups. Among stage III NSCLC patients who received CCRT, there was a trend for poor survival in those who expressed PD-L1. Our analysis indicated that a combination of lack of PD-L1 expression and CD8+ TIL density was significantly associated with favourable survival in these patients. It is proposed that PD-L1 expression in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III NSCLC.

Tokito T ，Azuma K ，Kawahara A ，Ishii H ，Yamada K ，Matsuo N ，Kinoshita T ，Mizukami N ，Ono H ，Kage M ，Hoshino T ... -  《-》