Spatial downregulation of CD74 signatures may drive invasive component development in part-solid lung adenocarcinoma.

Pulmonary nodules with part-solid imaging features manifest during the progression from preinvasive to invasive lung adenocarcinoma. To define the spatial composition and evolutionary trajectories of early-stage lung adenocarcinoma, we combined spatial transcriptomics (ST) and pathological annotations from 20 part-solid nodules (PSNs), four of which were matched with single-cell RNA sequencing. Two malignant cell populations (MC1 and MC2) were identified, and a linear evolutionary relationship was observed. Compared to MC2, the pre-existing malignant MC1 exhibited a lower metastatic signature, corresponding to the preinvasive component (lepidic) on pathology and the ground glass component on PSN imaging. Higher immune infiltration was observed among MC1 regions in ST profiles, and further analysis revealed that macrophages may be involved in this process through the CD74 axis. This work provides deeper insights into the evolutionary process and spatial immune cell composition behind PSNs and highlights the mechanisms of immune escape behind this adenocarcinoma trajectory.

Neoadjuvant immunotherapy in patients with pulmonary lymphoepithelioma-like carcinoma.

OBJECTIVES: Neoadjuvant immunotherapy can be used to treat early-stage non-small-cell lung cancer; however, their effects on pulmonary lymphoepithelioma-like carcinomas (LELC) remain unclear. MATERIALS AND METHODS: Thirty-nine patients with stages I-III LELC were treated with chemotherapy (Chemo) or neoadjuvant immune-checkpoint inhibitors (ICIs) with or without chemo (IO) before radical-intent surgery. Short-term outcomes included objective response rate (ORR), major pathologic response (MPR), pathologic complete response (PCR), and event-free survival. For comparison, we used IO to treat 63 patients with pulmonary squamous cell carcinomas (SQC) and 47 with adenocarcinomas (ADC). Propensity score matching was analyzed to minimize bias. RESULTS: ORRs of the LELC-IO and LELC-Chemo groups were 62.5% and 42.9%, respectively (odds ratio, 2.2, 95% confidence interval, 0.423-11.678, p = 0.346). Seven (21.9%) and zero patients in LELC-IO and LELC-Chemo groups, respectively, reached PCR. MPR was identified in five (15.6%) of the 32 patients with LELC-IO. The 1-year progression-free survival rates were 96.9% and 71.4% in IO and Chemo groups, respectively (p > 0.05). However, no difference was observed in ORR, PCR, and MPR between LELC and SQC groups (ORR, 63.2% vs. 68.4%, p > 0.05; PCR, 21.1% vs. 47.4, p > 0.05; MPR, 42.1% vs. 57.9%, p > 0.05) and LELC and ADC groups (ORR, 58.8% vs. 41.2%, p > 0.05; PCR, 17.6% vs. 23.5%, p = 0.672; MPR, 29.4% vs. 47.1%, p > 0.05). The plasma Epstein-Barr virus (EBV) DNA level in a patient was altered posttreatment. CONCLUSION: Patients with LELC could be benefit from neoadjuvant immunotherapy. Distinct histological subtypes demonstrated comparable efficacy with respect to neoadjuvant immunotherapy.

Short-term outcome of neoadjuvant immunotherapy and chemotherapy in non-small cell lung cancer: A systematic review and meta-analysis.

Background: Previously reported results have shown promising efficacy of neoadjuvant immunotherapy for resectable non-small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemotherapy have yet been reported. The aim of the present study was to evaluate the superiority of neoadjuvant immunotherapy compared with standard neoadjuvant chemotherapy in resectable NSCLC in terms of short-term clinical outcomes and surgical outcomes. Methods: We searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, the ClinicalTrials.gov database, Web of Science, and abstracts derived from multiple major cancer meetings up to March 1, 2020. Short-term clinical outcomes (including objective response rate [ORR], major pathologic response, and pathologic complete response [pCR]) and surgical outcomes (including surgical resection rate and R0 resection rate) were reported. Data were summarized as the estimated pooled value of each evaluated index. The risk of bias of included studies was assessed using standard methods. Results: This systematic review and meta-analysis of 21 trials on neoadjuvant immunotherapy and neoadjuvant chemotherapy for NSCLC included 1795 patients. Patients who received Programmed death ligand 1 (PD-1/PD-L1) inhibitors (NeoIO) alone (13.3%; 95% confidence interval [CI], 9.0%-19.3%) had the lowest ORR compared with those who received NeoIO plus chemotherapy (CT) (62.5%; 95% CI, 54.4%-70.0%) or CT alone (41.6%; 95% CI, 36.8%-46.7%) (NeoIO vs CT, P < .001; NeoIO + CT vs CT, P < .001). Receipt of NeoIO + CT (36.2%; 95% CI, 19.2%-57.6%) was associated with an elevated pCR rate compared with receipt of NeoIO alone (10.6%; 95% CI, 6.5%-16.9%; P < .001) or standard CT (7.5%; 95% CI, 5.7%-9.8%; P < .001). Neoadjuvant CT (87.2%; 95% CI, 74.9%-94.0%) was associated with a lower R0 resection rate compared with NeoIO alone (92.7%; 95% CI, 83.4%-97.0%; P = .360) or NeoIO + CT (91.6%; 95% CI, 84.3%-95.7%; P = .409). Meta-regression showed that a higher proportion of stage III patients was correlated with decreased surgical resection and R0 resection rates, whereas no impact was observed with neoadjuvant immunotherapy. Conclusions: Current data suggest that compared with neoadjuvant chemotherapy, immunotherapy-based regimens may provide superior pathological response along with a higher rate of complete resection. Immunotherapy combined with chemotherapy in neoadjuvant chemotherapy may be a more favorable clinical option. Further randomized controlled trials are warranted to provide long-term results of neoadjuvant immunotherapy for localized NSCLC and help guide clinical practice.