bims-mesote 2023-12-31 papers

Issue of 2023–12–31
three papers selected by
Laura Mannarino, Humanitas Research

World J Nucl Med. 2023 Dec;22(4): 293-296

Extensive Skeletal Muscle Metastases in Malignant Pleural Mesothelioma Detected by FDG PET/CT.

Mustafa Yilmaz, Ozan Kandemir, Ediz Tutar.

Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from pleural mesothelial cells. Distant skeletal muscle metastasis is rare in MPM. A 54-year-old woman was diagnosed with epithelioid MPM and treated with surgery, chemotherapy, and radiotherapy 2 years ago. During follow-up, diffuse irregular pleural thickening with focal chest wall invasion in the right hemithorax and two small pleural thickenings in the left hemithorax were seen on control diagnostic contrast-enhanced computed tomography (CECT). Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) imaging was performed as part of restaging. PET showed diffusely increased FDG uptake in the recurrent right pleural tumor, and two hypermetabolic small metastatic foci in the contralateral pleura. In addition, multiple hypermetabolic areas of various sizes in various skeletal muscle localizations, suggestive of extensive muscle metastases were noted. Histopathologic study confirmed metastatic epithelioid MPM. FDG PET/CT revealed multiple muscle metastases which were not observed on earlier CECT and contributed to the visualization of more extensive metastatic involvements in the presented case with MPM. FDG PET/CT can detect rarely seen skeletal muscle metastases that are not visualized on diagnostic CT, and provides more accurate restaging of MPM.

Keywords: FDG PET/CT; contrast-enhanced CT; malignant pleural mesothelioma; skeletal muscle metastasis

DOI: https://doi.org/10.1055/s-0043-1774730

Cancer Sci. 2023 Dec 26.

Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells.

Hiroto Yoneda, Atsushi Mitsuhashi, Aito Yoshida, Hirokazu Ogino, Satoshi Itakura, Na Thi Nguyen, Hiroshi Nokihara, Seidai Sato, Tsutomu Shinohara, Masaki Hanibuchi, Shinji Abe, Mika K Kaneko, Yukinari Kato, Yasuhiko Nishioka.

Combination immunotherapy with multiple immune checkpoint inhibitors (ICIs) has been approved for various types of malignancies, including malignant pleural mesothelioma (MPM). Podoplanin (PDPN), a transmembrane sialomucin-like glycoprotein, has been investigated as a diagnostic marker and therapeutic target for MPM. We previously generated and developed a PDPN-targeting Ab reagent with high Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the effects of anti-PDPN Abs on various tumor-infiltrating immune cells and their synergistic effects with ICIs have remained unclear. In the present study, we established a novel rat-mouse chimeric anti-mouse PDPN IgG2a mAb (PMab-1-mG2a ) and its core-fucose-deficient Ab (PMab-1-mG2a -f) to address these limitations. We identified the ADCC and CDC activity of PMab-1-mG2a -f against the PDPN-expressing mesothelioma cell line AB1-HA. The antitumor effect of monotherapy with PMab-1-mG2a -f was not sufficient to overcome tumor progression in AB1-HA-bearing immunocompetent mice. However, PMab-1-mG2a -f enhanced the antitumor effects of CTLA-4 blockade. Combination therapy with anti-PDPN Ab and anti-CTLA-4 Ab increased tumor-infiltrating natural killer (NK) cells. The depletion of NK cells inhibited the synergistic effects of PMab-1-mG2a -f and CTLA-4 blockade in vivo. These findings indicated the essential role of NK cells in novel combination immunotherapy targeting PDPN and shed light on the therapeutic strategy in advanced MPM.

Keywords: CTLA-4; NK cell; immune checkpoint inhibitor; malignant pleural mesothelioma; podoplanin

DOI: https://doi.org/10.1111/cas.16046

BMJ Case Rep. 2023 Dec 23. pii: e255916. [Epub ahead of print]16(12):

Complete clinical remission of malignant peritoneal mesothelioma with systemic pemetrexed and bevacizumab in a patient with a BAP1 mutation.

Jimmy Lee, Jordan Turetsky, Elham Nasri, Sherise C Rogers.

Malignant peritoneal mesothelioma (MPeM) is a rare malignancy with historically poor prognosis. Recent research has started to reveal increasingly prevalent genetic mutations seen in this malignancy. Here, we report a case of complete clinical remission of unresectable, metastatic MPeM with systemic chemotherapy. Immunohistochemistry of our patient's malignant cytology sample showed loss of Breast Cancer Gene 1-associated protein-1 expression (BAP1). The patient had synchronous diagnoses of primary squamous cell carcinoma of the anus, benign schwannoma and meningioma. Following the completion of 18 cycles of pemetrexed and bevacizumab, the patient has remained in clinical remission for 8 months. We examine the unusual susceptibility of unresectable MPeM to systemic chemotherapy and attribute susceptibility to the molecular milieu created by mutations in multiple DNA repair pathways. We encourage increased testing for and analysis of mutations in DNA repair pathways to improve future treatment outcomes in this rare malignancy.

Keywords: Chemotherapy; Genetics; Oncology; Pericardial disease; Stomach wall

DOI: https://doi.org/10.1136/bcr-2023-255916