Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.

To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.

Clinically occult primary fallopian tube carcinoma presenting as a malignant pleural effusion.

We report the first known case of malignant pleural effusion (MPE) as the sole presenting feature of clinically occult primary fallopian tube carcinoma (PFTC). A 57-year-old healthy woman was admitted with dyspnea. Evaluation demonstrated a right pleural effusion, fluid of which was malignant. The immunohistochemical profile, including negative calretinin, favored metastatic adenocarcinoma over mesothelioma but could not identify the primary tumour site. Pleural biopsy was not pursued as it would not have helped localize the primary. Chest, abdomen and pelvic computed tomography (CT) demonstrated only borderline lymphadenopathy in the left para-aortic lymph node chain that was hypermetabolic on positron emission tomography. Ultrasound and CT showed normal adnexal anatomy. These findings, coupled with an elevated serum CA-125, prompted empiric neoadjuvant chemotherapy targeting epithelial ovarian carcinoma (EOC) followed by surgery, which revealed a tiny left PFTC with negative peritoneal washings. Sampled left para-aortic lymph nodes were positive. The pleural effusion resolved after chemotherapy. Malignant pleural disease without peritoneal involvement is more characteristic of PFTC than of EOC, in which MPE is common but almost always accompanies peritoneal carcinomatosis. The extensive lymphatic supply of the fallopian tube promotes distant metastasis of small, seemingly localized tumours. This case is a reminder that the clinician should not be dissuaded from considering carcinoma of Müllerian origin, especially PFTC, as the cause of a MPE even in the face of normal gynecologic imaging. Appropriately broad immunohistochemical staining and careful attention to even minimal lymphadenopathy can be invaluable in pinpointing the primary tumour site in such patients.