Molecular Imaging of PD-1 Unveils Unknown Characteristics of PD-1 Itself by Visualizing "PD-1 Microclusters".

Programmed cell death-1 (PD-1) is one of the most famous coinhibitory receptors that are expressed on effector T cells to regulate their function. The PD-1 ligands, PD-L1 and PD-L2, are expressed by various cells throughout the body at steady state and their expression was further regulated within different pathological conditions such as tumor-bearing and chronic inflammatory diseases. In recent years, immune checkpoint inhibitor (ICI) therapies with anti-PD-1 or anti-PD-L1 has become a standard treatment for various malignancies and has shown remarkable antitumor effects. Since the discovery of PD-1 in 1992, a huge number of studies have been conducted to elucidate the function of PD-1. Herein, this paper provides an overview of PD-1 biological findings and sheds some light on the current technology for molecular imaging of PD-1.

Evaluation of therapeutic PD-1 antibodies by an advanced single-molecule imaging system detecting human PD-1 microclusters.

With recent advances in immune checkpoint inhibitors (ICIs), immunotherapy has become the standard treatment for various malignant tumors. Their indications and dosages have been determined empirically, taking individually conducted clinical trials into consideration, but without a standard method to evaluate them. Here we establish an advanced imaging system to visualize human PD-1 microclusters, in which a minimal T cell receptor (TCR) signaling unit co-localizes with the inhibitory co-receptor PD-1 in vitro. In these microclusters PD-1 dephosphorylates both the TCR/CD3 complex and its downstream signaling molecules via the recruitment of a phosphatase, SHP2, upon stimulation with the ligand hPD-L1. In this system, blocking antibodies for hPD-1-hPD-L1 binding inhibits hPD-1 microcluster formation, and each therapeutic antibody (pembrolizumab, nivolumab, durvalumab and atezolizumab) is characterized by a proprietary optimal concentration and combinatorial efficiency enhancement. We propose that our imaging system could digitally evaluate PD-1-mediated T cell suppression to evaluate their clinical usefulness and to develop the most suitable combinations among ICIs or between ICIs and conventional cancer treatments.

Clinical impact of SUVmax of interstitial lesions in lung cancer patients with interstitial lung disease who underwent pulmonary resection.

Background: Acute exacerbation of interstitial lung disease often causes fatal respiratory deterioration in lung cancer patients with interstitial lung disease. Here, we examined whether the maximum standardized uptake value of a contralateral interstitial lesion was a predictive factor of acute exacerbation of interstitial lung disease within 30 days postoperatively in lung cancer patients with interstitial lung disease who underwent pulmonary resection. Methods: Overall, 117 consecutive lung cancer patients with interstitial lung disease who underwent pulmonary resection between August 2010 and April 2019 at the Kumamoto University Hospital were retrospectively analysed for the association between the maximum standardized uptake value of the contralateral interstitial lesions and interstitial lung disease parameters. Results: The median maximum standardized uptake value of contralateral interstitial lesions was 1.61, which was regarded as the cut-off point predictive of the incidence of acute exacerbation of interstitial lung disease. Eight patients developed postoperative acute exacerbation of interstitial lung disease. There was no significant association between the maximum standardized uptake value of the contralateral interstitial lesions and postoperative acute exacerbation of interstitial lung disease. The maximum standardized uptake value was weakly but significantly associated with lactate dehydrogenase levels (r=0.211, P=0.022), Krebs von den Lungen-6 (r=0.208, P=0.028), and % diffusing capacity for carbon monoxide (r=-0.290, P=0.002). Moreover, seven patients developed acute exacerbation of the interstitial lung disease during the clinical course after 30 postoperative days, and the incidence rate of acute exacerbation of interstitial lung disease was significantly higher in the high maximum standardized uptake value group (≥1.61) than in the low maximum standardised uptake value group (<1.61) (12.7% vs. 0%, P=0.002, Gray's test). Conclusions: Maximum standardized uptake value was not a predictor of postoperative acute exacerbation of interstitial lung disease in lung cancer patients with interstitial lung disease after pulmonary resection, but could be a predictive tool of an association with interstitial lung disease severity and activity markers.

Simultaneous surgical resection of cardiac myxoma and atypical thymic carcinoid: a case report.

BACKGROUND: Cardiac myxoma is the most common type of primary cardiac tumor, and thymic carcinoid is a rare neuroendocrine tumor. No previous reports have described surgical management of concomitant occurrence of these neoplasms. We report a case of simultaneous surgical resection in a patient with coexisting cardiac myxoma and atypical thymic carcinoid. CASE PRESENTATION: A 44-year-old Japanese woman underwent chest roentgenography revealing an abnormality in the mediastinum. Computed tomography revealed a 100 mm mass in the anterior mediastinum and also a 30 mm mass in the left atrium. The mediastinal tumor was diagnosed as atypical carcinoid by biopsy. Having completed resection of atypical thymic carcinoid, cardiac mass was successfully resected with careful consideration of minimizing operation time and optimizing patient safety and oncological treatment. The histopathological diagnosis of the cardiac mass was myxoma. No adjuvant chemotherapy was administered, and no recurrence was seen as of the 45 month follow-up. CONCLUSIONS: The simultaneous surgery of cardiac myxoma and atypical thymic carcinoid was feasible and effective. To the best of our knowledge, this is the first case report to describe one-stage treatment of these neoplasms.

[Necrotic Thymoma;Report of a Case].

A 36-year-old man, who had never been detected abnormalities on an annual chest X-ray check up, presented with a sudden onset of right-sided chest pain and fever. Contrast-enhanced computed tomography showed an anterior mediastinal mass with necrosis or hemorrhage and right pleural effusion. Neither computed tomography-guided biopsy nor video-assisted thoracic surgery (VATS) yielded definitive histological diagnosis due to insufficiency of the sample. For diagnosis and treatment, we performed thymectomy. Histopathologically, the tumor was almost entirely necrotic with few viable tumor cells on periphery. A diagnosis of B2 thymoma was rendered.

Long-term follow-up of ciliated muconodular papillary tumor of the lung by computed tomography: a case report.

Ciliated muconodular papillary tumor (CMPT) is an extremely rare pulmonary tumor and the clinical characteristics are still unknown. We report the preoperative long-term clinical course and changes in computed tomography (CT) findings of CMPT. A 60-year-old man underwent lower bilobectomy for squamous cell carcinoma in the right lower lobe 18 years before the surgery for CMPT. Twelve years before the surgery for CMPT, a 4-mm small ground glass nodule arose in the left lower lobe. The nodule gradually grew and became dense over time. Because it became mostly solid with central cavities, the patient underwent wedge resection and the tumor was diagnosed as CMPT. There were no recurrences 20 months after surgery. The preoperative CT findings of CMPT were similar to progressive preinvasive lesion, whereas it followed the benign clinical course. To the best of our knowledge, this is the first report on long-term preoperative follow-up of CMPT.