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Immune checkpoint blockade therapy, one of the most promising cancer immunotherapies, has shown remarkable clinical impact in multiple cancer types. Despite the recent success of immune checkpoint blockade therapy, the response rates in cancer patients are limited (~20-40%). To improve immune checkpoint blockade therapy, relevant preclinical animal models are an essential component in the development and testing of multiple combination approaches and strategies. Companion dogs naturally develop several types of cancer that in many respects resemble clinical cancer in human patients. Therefore, the canine studies of immuno-oncology drugs are convertible into knowledge that informs and prioritizes new immuno-oncology therapy in humans. The challenge has been, however, that immunotherapeutic antibodies that target canine immune checkpoint molecules, such as canine PD-L1, have not been commercially available. Here, we developed a new canine PD-L1 antibody as an immuno-oncology drug and characterized its functional and biological properties by multiple assays. Furthermore, the therapeutic efficacy of cPD-L1 antibodies was evaluated in our unique caninized PD-L1 mice. Altogether, these in vitro and in vivo data including an initial safety profile in laboratory dogs, support the development of our canine PD-L1 antibody as an immune checkpoint inhibitor for studies in dogs with naturally occurring cancer for translational research. In conclusion, our new therapeutic antibody and caninized PD-L1 mouse model will be an essential translational research tool in raising the success rate of immunotherapy in both dogs and humans. Citation Format: Wonkyung Oh, Alyssa Kim, Deepika Dhawan, Perry M. Kirkham, Deborah W. Knapp, Seung-Oe Lim. Development of a canine PD-L1 antibody and caninized PD-L1 mouse model: an essential translational research tool to raise the success rate of immunotherapy in humans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2969.

The objective of this systematic review is to synthesize the relevant literature published after 2016 to ascertain the current landscape of science that relates mild traumatic brain injury (mTBI) to the onset of Alzheimer's disease and related dementias (ADRD) and identify areas of need for future research. We conducted database searches and retrieved articles that were published after 2016 that utilized cognitive assessments to understand the relationship between mTBI and ADRD. We identified eight relevant articles in the review process, four of which presented a significant relationship between mTBI and disease or cognitive impairment outcomes. The studies included in this systematic review underscore the need for future research investigating a possible causal relationship between mTBI and ADRDs given the high prevalence of mTBI among brain injury patients and the lack of literature specifically addressing this issue. Future research should standardize the definitions of mTBI, AD, and ADRDs to create reliable and reproducible results that more comprehensively capture the nuances of this relationship.

SUMMARY Skin lesions associated with alpha1-antitrypsin deficiency are becoming better defined and understood. Deficiency in this major antiproteinase, which neutralizes multiple proteolytic enzymes ranging from collagenases and elastases to trypsin and chymotrypsin, thus results in significant tissue autodigestion. This anti-proteinase is secreted by activated lymphocytes and macrophages, suggesting the existence of homeostasis which titrates the release of proteolytic enzymes by these cells, and the adequate neutralization of these proteases in order to prevent excessive tissue autodigestion each time these inflammatory cells are activated. We report a patient with alpha1-antitrypsin deficiency who, following insect bites and cellulitis developed widespread itching and scratching, leading to widespread lesions of prurigo nodularis. The colonization of his multiple skin lesions with Staphylococcus aureus and the release of potent T cell mitogens, such as Protein A and enterotoxin A from the bacterial cell membrane may have resulted in the release of additional proteolytic enzymes by the activated lymphocytes and macrophages, without the concomitant secretion of alpha1-antitrypsin with subsequent aggravation of his pruritus. These concepts are supported by electron microscopic evidence of excessive tissue autodigestion, and by immunocytochemical data identifying the presence of T helper and T cytotoxic/suppressor lymphocytes as well as macrophages within the upper dermis.

The idiopathic type of angiosarcoma most commonly occurs on the face and scalp of elderly persons. This rare tumor can be highly aggressive; however, if the diagnosis is made at an early stage, while the tumor is still localized and has a size that is less than 10 cm, surgical excision is the treatment of choice. We report a case whereby Mohs micrographic surgery was used to treat angiosarcoma of scalp.