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The PEOPLE trial aimed to identify new immune biomarkers in negative and low programmed death-ligand 1 (PD-L1) (0%-49%) advanced non-small-cell lung cancer (aNSCLC) patients treated with first-line pembrolizumab. Here we report the main outcomes and the circulating immune biomarkers analysis.The primary endpoint of this phase II trial was the identification of immune biomarkers associated with progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety were secondary endpoints. Absolute cell counts for 36 subsets belonging to innate and adaptive immunity were determined by multiparametric flow cytometry in peripheral blood at baseline and at first radiologic evaluation. An orthoblique principal components-based clustering approach and multivariable Cox regression model adjusted for clinical variables were used to analyze immune variables and their correlation with clinical endpoints.From May 2018 to October 2020, 65 patients were enrolled. After a median follow-up of 26.4 months, the median PFS was 2.9 months [95% confidence interval (CI) 1.8-5.6 months] and median OS was 12.1 months (95% CI 8.7-17.1 months). The ORR was 21.5%, DCR was 47.7% and median DoR was 14.5 months (95% CI 6.4-24.9 months). Drug-related grade 3-4 adverse events were 9.2%. Higher T cell and natural killer (NK) cell count at baseline and at the first radiologic evaluation were associated with improved PFS, DCR and OS. On the contrary, higher myeloid cell count at baseline or at the first radiologic evaluation was significantly associated with worse OS and DCR.Circulating immune biomarkers can contribute to predict outcomes in negative and low PD-L1 aNSCLC patients treated with first-line single-agent pembrolizumab.

Background To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. Methods Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. Results NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. Conclusions We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC., Highlights • Immunotherapy/chemoimmunotherapy combinations are currently not superior to immunotherapy alone for high PD-L1 aNSCLC. • NLR with a cut-off of 4 was validated as an independent prognostic factor for immunotherapy in high PD-L1 aNSCLC. • The addition of either PD-L1 ≥ 80% or LDH < 252 U/l to NLR < 4 did not result in better prognostic stratification. • The LIPS-3 is a validated 3-class prognostic classification based on the NLR, ECOG PS and pretreatment steroids. • The LIPS-3 is a routinely assessable adjuvant prognostic tool for high PD-L1 aNSCLC patients.

Here we show how anatomical and functional data recorded from patients undergoing stereo-EEG can be used to decompose the cortical processing following nerve stimulation in different stages characterized by specific topography and time course. Tibial, median and trigeminal nerves were stimulated in 96 patients, and the increase in gamma power was evaluated over 11878 cortical sites. All three nerve datasets exhibited similar clusters of time courses: phasic, delayed/prolonged and tonic, which differed in topography, temporal organization and degree of spatial overlap. Strong phasic responses of the three nerves followed the classical somatotopic organization of SI, with no overlap in either time or space. Delayed responses presented overlaps between pairs of body parts in both time and space, and were confined to the dorsal motor cortices. Finally, tonic responses occurred in the perisylvian region including posterior insular cortex and were evoked by the stimulation of all three nerves, lacking any spatial and temporal specificity. These data indicate that the somatosensory processing following nerve stimulation is a multi-stage hierarchical process common to all three nerves, with the different stages likely subserving different functions. While phasic responses represent the neural basis of tactile perception, multi-nerve tonic responses may represent the neural signature of processes sustaining the capacity to become aware of tactile stimuli., Highlights • StereoEEG shows different time courses in responses to peripheral nerve stimulations. • Strong phasic responses likely reflect thalamic input into primary somatosensory cortex. • Delayed responses subserve sensorimotor synergies in motor and premotor cortex. • Tonic multi-nerve responses in perisylvian region may be markers of tactile awareness.

Background Thymic Epithelial Tumors (TETs) are rare entities, which can be diagnostic challenges for Pathologists. It has been proven that patients’ referral to a Center with an expert Pathologist is a key factor in obtaining the correct diagnosis. As therapeutic options vary widely for the different entities of TET spectrum, an accurate diagnosis is essential in the therapeutic planning. We aimed at investigating this topic, analyzing pathologic second opinions in a single reference Centre. Methods We retrospectively reviewed all the cases which obtained a pathologic second opinion, after being diagnosed elsewhere with a TET or for a suspicion of TET, at the Istituto Nazionale dei Tumori (INT), Milan, Italy, between 2010 and 2019. Descriptive statistics were used for qualitative variables. Concordance between diagnoses was estimated through Cohen’s k. Results We identified 278 cases; 72 of them received a pathologic revision in INT. Among these cases, initial diagnosis was thymoma A in 5 cases, thymoma AB in 3 cases, thymoma B1 in 5 cases, thymoma B2 in 15 cases, thymoma B3 in 7 cases, thymoma Not Otherwise Specified (NOS) in 8 cases, thymic carcinoma in 17 cases, carcinoma NOS in 8 cases, carcinoma with different histology in 3 cases, lymphoblastic lymphoma in one case. INT pathologic revision changed the diagnosis in 41 (56.9%) cases, with a potential shift in therapeutic approach in 32 (44.4%). In particular, 12 cases of carcinoma NOS or lymphoma were reviewed as thymic carcinoma (10 cases) or thymoma (2 cases); 9 cases of thymic carcinoma were reviewed as cases of thymoma (7 B3, 2 B2); 11 cases of thymoma were reviewed as different thymoma subtypes (9 cases), or thymic carcinoma (one case), or diffuse large B cell lymphoma (one case). Concordance between Pathologists was moderate when the initial diagnosis was thymoma (74.7%, k 0.447), only slight when the initial diagnosis was thymic carcinoma (60.5%, k 0.139). Conclusions A change in histological characterization was documented in a significant percentage of cases initially diagnosed in other Centers, not rarely with potential therapeutic implications. Therefore, in the approach to TETs as well as for other rare diseases, patients’ referral to a reference Centre with high pathology expertise is strongly recommended. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure C. Proto: Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. D. Signorelli: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS. F.G.M. de Braud: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer-Ingelheim; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: F. Hoffmann-La Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Sharp and Dohme; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Merck Serono; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer. M.C. Garassino: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD International GmbH; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim Italia S.p.A; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ignyta; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Incyte; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Inivata; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: MedImmune; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (institution): Tiziana; Honoraria (institution): Foundation Medicine; Research grant / Funding (institution): AIRC; Research grant / Funding (institution): AIFA; Research grant / Funding (institution): Italian Moh; Research grant / Funding (institution): Transcan. G. Lo Russo: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. All other authors have declared no conflicts of interest.

Background Real-world data regarding clinical outcomes associated with first-line pembrolizumab (pembro) monotherapy among specific subgroups of NSCLC patients are lacking. Methods A comprehensive clinicopathological database of patients with NSCLC and PD-L1>50% treated with frontline pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created. Post-progression outcomes have been previously reported. Clinical outcomes in specific subgroups of interest are presented in the current report. Analysis was performed using the SAS 9.3 software. Multivariate analysis was performed with the Cox regression model. Results Among 173 eligible patients, median age at diagnosis was 68 years, 65% were male, 88% were current or former smokers, 25% had an ECOG PS > =2, histology was 67% adeno, 21% squamous, 20% had brain mets, 15% had liver mets at diagnosis and 28% received steroids at the beginning and/or during treatment. Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. Hazard Ratios for OS, with corresponding 95% CIs and p-values for specific subgroups were as follows: Elderly patients ( >70 years): HR = 0.85 (0.52-1.38), p = 0.51; Brain mets: HR = 1.17 (0.63-2.18), p = 0.63; Stage I-IIIC: HR = 0.56 (0.22-1.39), p = 0.21; PS > =2: HR = 1.73 (1.55-1.84), p Conclusions Real-world data in a large retrospective cohort of patients with NSCLC and PD-L1>50% indicate that 1) Pembro frontline is also active in inoperable stage I-IIIC patients, 2) Elderly patients (>70 years) derive similar survival benefit to younger ones, except from those with PS > =2, 3) Steroid use at the beginning and/or during treatment is associated with a three-fold increase in the risk of death. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure G. Mountzios: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca Greece; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Greece; Honoraria (self), Travel / Accommodation / Expenses: Pfizer Hellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD Hellas; Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Greece. G. Banna: Advisory / Consultancy: Janssen; Advisory / Consultancy: Boehringer; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Ipsen. A. Christopoulou: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PFIZER; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: NOVARTIS. H. Linardou: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Boehringer ; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. A. Calles: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS. A. Addeo: Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: BMS. P.A. Kosmidis: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Leo. M.C. Garassino: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche ; Honoraria (self), Advisory / Consultancy: PFIZER; Honoraria (self): MEDSCAPE; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD Hellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): GSK. All other authors have declared no conflicts of interest.

StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ( $$

Background Hyponatremia (serum sodium concentration [Na+] Methods ASSERT was a prospective, observational, non-interventional study conducted from October 2015 to June 2017 in cancer patients requiring treatment for hyponatremia secondary to SIADH at 18 Italian oncology centres. Management of hyponatremia primarily included water restriction, tolvaptan and hypertonic saline, in accordance with local standard of care/guideline recommendations. The primary endpoint was change in serum [Na+] from baseline visit to end of the first month of the observational period, or earlier discontinuation. Results The full analysis set (FAS) included 68 adult cancer patients (lung cancer, n = 48, SCLC, n = 33). Group 1 patients received ≥1 dose of tolvaptan during the observational period; Group 2 patients did not receive tolvaptan. Overall survival (FAS) was significantly higher in Group 1 vs Group 2 (median 123 vs 56 days; p = 0.001), as was mean survival (299.4 vs 74.9 days; p = 0.001). In a linear regression analysis of the relationship between sodium levels and tolvaptan dose intensity for the lung cancer and SCLC cohorts, dose intensity correlated significantly with clinical response after 6 months of treatment in both cohorts (p = 0.005 and p = 0.023, respectively). In the lung cancer cohort, a significantly higher percentage of patients achieved serum [Na+] ≥130 mmol/L in Group 1 vs Group 2 during 6 months of follow-up (Group 1, 87.5% vs Group 2, 62.5%; p = 0.033). These results were similar to those observed in the FAS. Conclusions Hyponatremia secondary to SIADH is a potentially modifiable risk factor, which might be implicated in the survival of lung cancer patients. Correction of hyponatremia may be preferentially achieved with pharmacological treatment, rather than the non-pharmacological approaches routinely used in clinical practice. Clinical trial identification NCT102573077. Editorial acknowledgement Sarah Stowell PhD, CMPP of Ashley Medical Communications, funded by Otsuka Pharmaceutical Europe Ltd. Legal entity responsible for the study Otsuka Pharmaceutical Italy Srl. Funding Otsuka Pharmaceutical Italy Srl. Disclosure R. Berardi: Honoraria (self), Advisory / Consultancy: Otsuka Pharmaceutical. C. Ferrara: Full / Part-time employment: Otsuka Pharmaceutical Italy. M.G. Giustra: Full / Part-time employment: Otsuka Pharmaceutical Italy. R. Evans: Full / Part-time employment: Otsuka Pharmaceutical Europe. All other authors have declared no conflicts of interest.

Background The DiMaio (D), EPSILoN (E) and plasma microRNA signature classifier (MSC), are 3 diverse clinico-biochemical and molecular scores able to independently predict prognosis in advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with immunotherapy (IO). By assessing the ability of each test a combined score (SC) called DEMo was developed. The study aims to prospectively evaluate the prognostic value of DEMo in aNSCLC pts treated with IO. Methods We included in the analyses 166 aNSCLC pts treated in 1L (n = 47) and further-lines (n = 119) with IO at Istituto Nazionale Tumori of Milan. For all pts we obtained complete necessary data for both clinical SC: D (sex, histology, ECOG-PS stage, uses of platinum-based therapy at 1L and response to 1L) and E (ECOG-PS, Smoke, Liver, LDH, NL-ratio). MSC was prospectively evaluated in plasma samples collected at baseline IO and the risk level was assessed. Endpoints were median overall survival (mOS), progression-free survival (mPFS) and overall response rate (ORR). Kaplan-Meier and Cox model were used to generate survival curves and multivariate analyses, respectively. Results In multivariate analysis adjusted for age, sex, smoke and ECOG-PS each score remain independently significant for both PFS (D: HR = 1.99, CI95% 1.21–3.03, p = 0.007; E: HR = 1.87 CI95% 1.12 – 3.10, p = 0.016; MSC: HR = 1.56, CI95% 1.03–2.37, p = 0.0370) and OS (D: HR = 3.12, CI95% 1.80–5.41, p = 0.0001; E: HR = 2.21, CI95% 1.28–3.79, p = 0.0041; MSC: HR = 2.03, CI95% 1.30–3.17, p = 0.0019). DEMo separated patients in 4-risk groups (gr) based on the presence of 3–2–1–0 poor prognostic SC. Strata had 0%–7%–20%–46% 18 months (mo) PFS (p Conclusions We created a composite clinic-molecular combined biomarker classifier able to better predict prognosis compared to each single SC and to select patients who less likely benefit from IO. DEMo could be a useful tool to guide choices in aNSCLC. Clinical trial identification The authors. Legal entity responsible for the study Fondazione IRCCS Istituto Nazionale Tumori of Milan, Italy. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background CD73 is an enzyme involved in the conversion of extracellular AMP into adenosine. Adenosine inhibits T lymphocytes, contributing to immune escape. CD73 promotes proliferation and migration and has been associated to a negative prognosis in various cancers. Data are limited on its role in metastatic NSCLC, particularly with genetic drivers. Methods We collected patients (pts) with EGFR Mutant (EM), ALK Rearranged (AR) and Wild Type (WT) metastatic NSCLC treated outside trials at our Institution between 2010 and 2018. Cases without tissue samples were excluded. CD73 expression was determined by immunohistochemistry (Ab133582 ABCAM). Semiquantitative H score (HS) was calculated multiplying the membrane intensity score (0-3) by the % of stained cells to yield a value of 0–300. Median value of HS was chosen as a cutoff. Overall Survival (OS) was estimated through Kaplan-Meier method. After a gene expression profiling on TCGA NSCLC datasets (n = 488), we divided EM, AR, WT cases according to CD73 median level. Cibersort analysis was performed in these series to profile the immune infiltrate. Results Fifty-four EM, 28 AR and 40 WT NSCLCs were identified. Median HS was 0 for EM and WT, 100 for AR cases. No imbalances in CD73 expression emerged according to main clinico-pathological variables. EM pts with a high HS showed a trend towards a worse OS (23.4 vs 39.5 months, p .2237); on the contrary, high HS had a non-significant positive prognostic role in AR (53.3 vs 25.1 months, p .1263) and WT pts (59.6 vs 18.7 months, p .5063). In accordance with our data, we observed some differences among the CD73 high subgroups profiling infiltrate of TCGA cases: WT were enriched in Treg and resting dendritic cells (DC), AR showed an increase in M1 macrophages, EM had a reduction in activated NK cells along with an increase in activated DC. Nanostring is ongoing on our series. Conclusions CD73 expression seems to have a different prognostic role for EM, AR and WT metastatic NSCLC. In particular, the trend towards a better outcome for AR cohort is a novel finding, potentially supported by a specific inflammatory infiltrate. Despite the small number of analyzed cases, CD73 role in NSCLC different subgroups warrants further investigation. Nanostring results will be presented. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure G. Lo Russo: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Travel / Accommodation / Expenses: Eli Lilly. D. Signorelli: Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (self), Travel / Accommodation / Expenses: BMS. F.G.M. de Braud: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer-Ingelheim; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: F. Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Sharp and Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer. M.C. Garassino: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): MSD International GmbH; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim Italia S.p.A; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Ignyta; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Inivata; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): MedImmune; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (institution), Research grant / Funding (institution): Tiziana; Honoraria (institution), Research grant / Funding (institution): Foundation Medicine; Research grant / Funding (self): AIRC; Honoraria (institution): AIFA; Honoraria (institution): Italian Moh; Honoraria (institution): Transcan. C. Proto: Honoraria (self), Travel / Accommodation / Expenses: MSD International GmbH; Honoraria (institution), Travel / Accommodation / Expenses: BMS; Honoraria (institution), Travel / Accommodation / Expenses: Eli Lilly. All other authors have declared no conflicts of interest.