Tertiary lymphoid structures (TLS) existence is correlated with favorable prognosis in many types of cancer including non-small cell lung cancer (NSCLC). However, TLS formation and its relationship with treatment response remains unknown in NSCLC who received anti-PD-1 antibody plus chemotherapy as the neoadjuvant treatment (neoadjuvant chemoimmunotherapy). Here, we investigate TLS maturation and abundance in resectable NSCLC receiving neoadjuvant treatments. We retrospectively collected formalin-fixed paraffin embedded (FFPE) tissues from patients with resectable NSCLC (stage II–IIIA) from three cohorts based on treatment: naïve (N=40), neoadjuvant chemoimmunotherapy (N=40), and neoadjuvant chemotherapy (N=41). The TLS in tumor tissues was detected by immunohistochemical staining, and the differences in TLS maturation and abundance among different treatment groups were analyzed, as well as the relationship with pathological response and prognosis of patients. Multiplex immunofluorescence staining was used to explore the features of immune microenvironment. Higher major pathological response (MPR) rate and pathological complete response (pCR) rate were in the neoadjuvant chemoimmunotherapy group than in the neoadjuvant chemotherapy group (MPR: 45.0% vs 17.1%; pCR: 35.0% vs 4.9%). Among the three cohorts, neoadjuvant chemoimmunotherapy-treated NSCLCs displayed highest TLS maturation and abundance. Both the maturation and abundance of TLS were significantly correlated with MPR in both the neoadjuvant chemoimmunotherapy and the chemotherapy group. Patients with high maturation and abundance of TLS exhibited better disease-free survival (DFS) in all the three cohorts. TLS maturation was also an independent predictor for DFS in the neoadjuvant chemoimmunotherapy and treatment naïve group. Multiplex immunohistochemistry analysis using paired biopsy-surgery samples showed increased infiltration of CD8+T cell and decreased infiltration of M1 and M2 macrophages after neoadjuvant chemoimmunotherapy treatment in patients achieving MPR. There were no significant differences in features of immune cell infiltration for those with mature TLS achieving MPR when cross-compared across the three cohorts. These results demonstrate that TLS maturation is associated with MPR and an independent predictor for DFS in resectable neoadjuvant chemoimmunotherapy-treated NSCLC. The induction of TLS maturation may be a potential mechanism of action of neoadjuvant chemoimmunotherapy in resectable NSCLC.

PurposeThe aim of our study was to investigate the value of baseline and preoperative neutrophil-to-lymphocyte ratio (NLR) in predicting the pathological response and disease-free survival (DFS) of neoadjuvant chemotherapy alone or combined with programmed cell death-1 (PD-1) checkpoint inhibitors in patients with resectable non‒small cell lung cancer (NSCLC).Materials and MethodsResectable NSCLC patients who underwent neoadjuvant chemotherapy alone or combined with PD-1 checkpoint inhibitors between January 2018 and January 2020 were included. Peripheral venous blood samples of the patients were collected within 3 days prior to the first neoadjuvant treatment and within 3 days prior to surgery.ResultsA total of 79 patients in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group and 89 patients in neoadjuvant chemotherapy alone group were included. Thirty-five point four percent of the patients achieved pathological complete response (pCR) in neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group, whereas only 9.0% reached pCR in the group of neoadjuvant chemotherapy. High NLR level were correlated with poor pathological response and DFS in neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors group. Multivariate analysis revealed that baseline NLR could independently predict pathological response and DFS in the neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors group. ConclusionHigh NLR level were correlated with poor pathological response and shorter DFS in patients with NSCLC undergoing neoadjuvant chemotherapy or combined with PD-1 checkpoint inhibitors. Meanwhile, baseline NLR could independently predict response to pathological response and DFS, revealing its potential as a screening tool in NSCLC patients who received neoadjuvant chemotherapy combined with PD-1 checkpoint inhibitors.

Background We aimed to develop a prognostic nomogram based on a new classification of combined micropapillary and solid components in pathological stage IA invasive lung adenocarcinoma (LUAD). Methods According to the total proportion of solid and micropapillary components (TPSM), the X‐tile software was applied to classify patients into the following three groups: TPSM‐low (TPSM‐L), TPSM‐middle (TPSM‐M), and TPSM‐high (TPSM‐H). The postoperative survival was compared among the three groups. The multivariate Cox regression analysis was performed to identify independent prognostic factors for survival. According to these factors, a nomogram model was developed to provide a personalized prognostic evaluation. Results A total of 595 patients with pathological stage IA invasive LUAD were included in our study. The 5‐year disease‐free survival and overall survival rates in patients with TPSM‐H and TPSM‐M were significantly lower than those with TPSM‐L. The multivariate Cox regression analysis revealed that the TPSM classification was an independent prognostic factor for survival. According to TPSM classification, we developed a nomogram model which had good calibration and reliable discrimination ability to evaluate survival. Conclusions The nomogram based on the combination of micropapillary and solid components has good prognostic value in predicting postoperative recurrence and survival of patients with pathological stage IA invasive LUAD.

Background To investigate the prognostic significance of station 4R lymph node (LN) dissection in patients who underwent operations for right primary non-small cell lung cancer (NSCLC). Methods We performed a retrospective study involving patients with right primary NSCLC who received lobotomy or pneumonectomy with mediastinal LN dissection between January 2011 and December 2017. Propensity score matching was performed. Disease-free survival (DFS) and overall survival (OS) were compared between patients with and without station 4R dissection. Results Our study included 2070 patients, with 207 patients having no station 4R dissection (S4RD− group) and 1863 patients having station 4R dissection (S4RD+ group). The 4R LN metastasis rate was 13.4% (142/1748), higher than that for other mediastinal LN metastases. Compared with the S4RD− group, the S4RD+ group had higher 5-year DFS (48.1% vs. 39.1%, P = 0.009) and OS (54.4% vs. 42.8%, P = 0.025). Station 4R dissection was an independent risk factor for DFS (odds ratio, OR, 1.28, 95% confidence interval, CI, 1.08–1.64, P = 0.007) and OS (OR 1.31, 95% CI 1.04–1.63, P = 0.018). Patients with adjuvant chemotherapy had a better prognosis after station 4R dissection than those without adjuvant chemotherapy (57.4% vs. 52.3%, P = 0.006). The 5-year OS in the station 4R metastasis group was lower than that in the station 4R non-metastasis group (26.9% vs. 44.3%, P = 0.006) among N2 patients. The 5-year OS of the single-station 4R metastasis group was lower than that of the single-station 7 metastasis group (15.7% vs. 51.6%, P = 0.002). Conclusions Station 4R metastasis was the highest among all the mediastinal station metastases in right primary NSCLC patients. Station 4R dissection can improve the prognosis and should be recommended as a routine procedure for these patients.

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