Insight into the significance of Foxp3 + tumor-infiltrating lymphocytes in squamous cell lung cancer.

PURPOSE: Although developing a better understanding of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) might provide essential knowledge to predict response to immunotherapy and prognosis, our current knowledge about Foxp3 + TILs is inadequate. This study investigated the prognostic significance of tumor-infiltrating Foxp3 + lymphocytes (Foxp3 + TILs) in squamous cell lung cancer (SQ-LC) objectively. METHODS: Among patients with SQ-LC surgically resected in our institution between 2011 and 2017, those with pathological stage IA3-IIIA were immunohistochemically studied to evaluate Foxp3 + TILs in their tumor stroma. The impact of Foxp3 + TILs on relapse-free survival (RFS) was analyzed with Kaplan-Meier survival analysis and multivariate analysis using a Cox proportional hazards model/Fine-Gray model. RESULTS: This study analyzed 100 patients. Multivariate analysis showed that a large number of Foxp3 + TILs in the stroma does not associate with a poor prognosis, rather that a large number of Foxp3 + TILs (≥ 64 cells) tend to be associated with a more favorable prognosis than a small number of Foxp3 + TILs (< 64 cells) (large vs small number: HR, 0.56; 95% CI, 0.17-1.83; P = 0.34). Exploratory analysis also showed that in the two populations divided by a difference in Foxp3 expression levels, similar trends to the main analysis were observed. CONCLUSION: Our results showed that a large number of Foxp3 + TILs in the stroma may not associate with a poor prognosis in SQ-LC. To use the seemingly complicated information of Foxp3 + TILs as biomarkers, better understanding the diversity and heterogeneity of Foxp3 + TILs and analyzing their subpopulations that increase in the TME may be needed.

Insight into the significance of CD8+ tumor-infiltrating lymphocytes in squamous cell lung cancer.

BACKGROUND: Although there are great expectations regarding the use of tumor-infiltrating lymphocytes (TILs) to predict effects of immunotherapies and prognosis, knowledge about TILs remains insufficient for clinical application. METHODS: We objectively investigated the prognostic significance of tumor-infiltrating CD8 + lymphocytes (CD8 + TILs) in squamous cell lung cancer (SQ-LC). Among patients who underwent surgical resection of SQ-LC in 2011-2017, 100 patients with pathological stage IA3-III were immunohistochemically studied to evaluate CD8 + TILs in the tumor stroma and parenchyma. The impact of CD8 + TILs on relapse-free survival was analyzed using a Kaplan-Meier survival analysis and multivariate analyses using Fine-Gray and Cox proportional hazards models. RESULTS: The multivariate analysis showed that large and small numbers, but not intermediate numbers, of CD8 + TILs in the tumor stroma may be related to a more favorable prognosis (small vs. intermediate: HR, 0.64; 95% CI: 0.29-1.41, p = 0.27; large vs. intermediate: HR, 0.48; 95% CI: 0.21-1.09, p = 0.08). In contrast, a large number of CD8 + TILs in the tumor parenchyma was associated with a poor prognosis (HR, 2.60; 95% CI: 0.91-7.42, p = 0.075). An exploratory analysis showed a potentially strong association between an extremely large number of CD8 + TILs in the tumor parenchyma and a poor prognosis, even with a large number of CD8 + TILs in the tumor stroma. CONCLUSION: Our study provided partial but important information on the significance of CD8 + TILs in SQ-LC. To use CD8 + TILs as biomarkers, a better understanding of CD8 + TILs as well as other important components in the tumor microenvironment and the inflammatory phenotypes they form may be needed.

Examination of the effectiveness of local therapy for oligo-recurrence of EGFR-mutated NSCLC.

BACKGROUND: The effectiveness of local therapy has been reported in patients with oligo-recurrence of non-small cell lung cancer (NSCLC), a metachronous recurrence with a limited number of recurrences, which can be treated with local therapy. Conversely, remarkable progress has been made in systemic therapy for NSCLC with the advent of molecular targeted therapy. In particular, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are very effective in the treatment of EGFR-mutated NSCLC. There is currently no consensus on treatment for oligo-recurrence of EGFR-mutated NSCLC. METHODS: From 2004 to 2014, 811 patients underwent complete resection for NSCLC at Kitasato University Hospital and, of these, 244 patients developed recurrence. Oligo-recurrence was defined as the presence of two or less recurrent lesions, and 34 patients presented with EGFR-mutated oligo-recurrence. RESULTS: We retrospectively examined and compared the effects of EGFR-TKIs with those of radical local therapy in patients with oligo-recurrent EGFR-mutated NSCLC. The five-year post-recurrence survival (PRS) rates of patients with EGFR-mutated oligo-recurrence who received radical local therapy (n = 23) and those who did not (n = 11) were 59.4 and 45.5%, respectively (p = 0.777). Multivariate analysis revealed no favorable prognostic factors associated with prolonged PRS, and radical local therapies did not improve PRS in patients with oligo-recurrence (p = 0.551). CONCLUSION: Radical local therapy did not affect PRS in patients with oligo-recurrent EGFR-mutated NSCLC. Even in cases of oligo-recurrence, the administration of local therapy in patients with EGFR-mutated NSCLC might be carefully considered.

Ciliated muconodular papillary tumors of the lung: Cytologic features and diagnostic pitfalls in intraoperative examinations.

Ciliated muconodular papillary tumors (CMPTs) of the lung are rare, likely benign neoplastic lesions. Here we describe a case of a CMPT, focusing on its cytologic features, which to our knowledge have not been reported previously. Owing to dull back pain, a 69-year-old male non-smoker underwent CT, which revealed a 1.3 × 1.3-cm solid nodule in the peripheral field of the left lower lung lobe. A wedge resection of the nodule was performed, with the provisional diagnosis being primary lung cancer. Macroscopic examination of a resected specimen showed a 1.2-cm grayish nodule. Touch imprint smear cytology revealed ciliated columnar cells and mucous cells, as well as abundant extracellular mucin on inflammatory background of lymphocytes and histiocytes. Histologic examination revealed a nodular papillary tumor composed of ciliated columnar cells, mucous cells, and basal cells surrounded by a mucin pool. No nuclear atypia or mitotic figures were identified. The final diagnosis was CMPT. The postoperative course was uneventful, with no recurrence at 8 months after surgery. Although a CMPT is a rare lung tumor, it should be considered when cytological or histological examination of a solitary peripheral lung nodule shows non-atypical ciliated cells and mucous cells surrounded by mucin.