Abstract 1783P
Background
Lung cancer (LC) tissue for immunological characterization is often scarce, mostly due to diagnosis at advanced stage. We assessed if BAL during diagnostic workup may serve for investigation of tumor immune microenvironment (TME), with implications on disease and treatment outcome.
Methods
BAL and blood were collected during bronchoscopy for diagnostic and/or therapeutic purposes in consecutive patients with monolateral primary lesion. T cell status in the tumor BAL (t-BAL) was assessed with flow cytometry and compared with contralateral BAL (cl-BAL) and peripheral blood. We profiled lymphocytes (T, B, NK) and T cell subsets (naive, memory, and terminally differentiated T-cell subsets), along with the expression of PD1, ICOS1, and CD28. Within CD4 T cells, Th1, Th2, and Th17 and regulatory T-cells (T-regs) were also studied.
Results
33 patients underwent BAL and blood sampling. Of those, 21 had histologically-confirmed LC (11 squamous, 5 adenocarcinoma,1 poorly differentiated, 4 small cell LC). All pts were at III-IV TNM stage. PD-L1 was available in 11 cases, with a median value of 1% (IQR 0-65). Nineteen/21 pts received active treatment after BAL, of whom 4/19 immunotherapy, alone or as consolidation after chemo-RT. BAL/blood samples were 63. As expected, % tot lymphocyte in blood was higher than in t- and cl-BAL with greater % of B and NK cells. CD8 T cells were significantly enriched in t-BAL vs blood (41.1% vs 28.8% p=0.007). No differences were noted in %CD4 across t-, cl-BAL and blood. Polarized effector functions of CD8 T cells in t-BAL were suggested by higher levels of PD-1+ terminally differentiated (47.3% vs 30.1% in blood, p=0.02) and PD-1+ effector memory T-cells (69.4% vs 36.9% in blood, p<0.001). As for CD4 T cells, normalized T-regs were higher in both t- and cl-BAL vs blood (4.13% and 3.22%, vs 1.21%, p=0.001), while normalized Th1 were significantly higher in t-BAL vs vs cl-BAL (6.5% vs 3.9%, p=0.03).
Conclusions
To our knowledge, this is one of the first reports to investigate TME in BAL of LC pts. BAL better reflected T cell functional status in LC TME, compared to blood. Combined BAL and blood analysis may be an effective tool for discovery of response and toxicity biomarkers, with particular regard to immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Silvia Novello.
Funding
Has not received any funding.
Disclosure
M. Di Maio: Financial Interests, Personal and Institutional, Sponsor/Funding: Tesaro-GlaxoSmithKline; Financial Interests, Personal and Institutional, Advisory Role: Novartis; Financial Interests, Personal and Institutional, Advisory Role: Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Eisai; Financial Interests, Personal and Institutional, Advisory Role: Takeda; Financial Interests, Personal and Institutional, Advisory Role: Janssen; Financial Interests, Personal and Institutional, Advisory Role: Astellas; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca. P. Bironzo: Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: BMS; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: BeiGene; Financial Interests, Personal and Institutional, Advisory Role: Roche. M.L. Reale: Financial Interests, Personal and Institutional, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal and Institutional, Speaker’s Bureau: Boehringer Ingelheim. F. Passiglia: Financial Interests, Personal and Institutional, Advisory Role: MSD; Financial Interests, Personal and Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca. E. Capelletto: Financial Interests, Personal and Institutional, Advisory Board: AZD; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Advisory Board: Bhoeringer Ingelheim. S. Novello: Financial Interests, Personal and Institutional, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal and Institutional, Speaker’s Bureau: MSD; Financial Interests, Personal and Institutional, Speaker’s Bureau: Roche; Financial Interests, Personal and Institutional, Speaker’s Bureau: BMS; Financial Interests, Personal and Institutional, Speaker’s Bureau: Takeda; Financial Interests, Personal and Institutional, Speaker’s Bureau: Pfizer; Financial Interests, Personal and Institutional, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal and Institutional, Speaker’s Bureau: Boehringer Ingelheim. All other authors have declared no conflicts of interest.