Year-end Sale % OFF 
Abstract
BackgroundThis study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients.MethodsUninvolved regional lymph node sections from 67 patients with stage I–III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment.ResultsCD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01). Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049) and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055). The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively).ConclusionsMyeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted.
Highlights
Lung cancer is the most frequent cause of cancer death in the United States.[1]
Myeloid clusters are prominent and overall signal transducer and activator of transcription 3 (STAT3) activity is dramatically elevated in uninvolved non-small cell lung cancer (NSCLC) regional lymph nodes
By IHC staining, we found that the myeloid cells associated with anthracosis usually formed clusters, which was not observed in normal lymph nodes (LNs) (Fig. 2B)
Summary
Lung cancer is the most frequent cause of cancer death in the United States.[1] Despite reduced smoking rates, cigarette smoke is still the main risk factor associated with lung cancer.[2] Tobacco smoke contains thousands of chemicals, about 70 of which are known carcinogens.[3] Anthracosis, which is the deposition of black dust matter, has been found in the lungs and lymph nodes (LNs) of those with a history of smoking.[4] Exposure to tobacco smoke induces mutagenesis leading to the development of lung cancer, and continued smoking causes increased mortality and recurrence in early stage disease.[5] therapies are available for the treatment of non-small cell lung cancer (NSCLC), most patients develop recurrence due to its highly invasive and metastatic capacity. This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
