The San Cristóbal Galapagos tortoise, Chelonoidis chathamensis, is native to San Cristóbal, the most eastern and oldest island of the Galapagos Archipelago. Although numerous studies on the ecology, behavior and genetics of Galapagos tortoises have been published, little is known about the health status of these animals. Here we report blood values from clinically healthy tortoises.

The 2019 annual National Toxicology Program Satellite Symposium, entitled “Pathology Potpourri,” was held in Raleigh, North Carolina, at the Society of Toxicologic Pathology’s 38th annual meeting. The goal of this symposium was to present and discuss challenging diagnostic pathology and/or nomenclature issues. This article presents summaries of the speakers’ talks along with select images that were used by the audience for voting and discussion. Various lesions and topics covered during the symposium included aging mouse lesions from various strains, as well as the following lesions from various rat strains: rete testis sperm granuloma/fibrosis, ovarian cystadenocarcinoma, retro-orbital schwannoma, periductal cholangiofibrosis of the liver and pancreas, pars distalis hypertrophy, chronic progressive nephropathy, and renal tubule regeneration. Other cases included polyovular follicles in young beagle dogs and a fungal blood smear contaminant. One series of cases challenged the audience to consider how immunohistochemistry may improve the diagnosis of some tumors. Interesting retinal lesions from a rhesus macaque emphasized the difficulty in determining the etiology of any particular retinal lesion due to the retina’s similar response to vascular injury. Finally, a series of lesions from the International Harmonization of Nomenclature and Diagnostic Criteria Non-Rodent Fish Working Group were presented.

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Introduction: Rhesus macaques share extensive similarities with humans including immune cell populations, regulatory mechanisms, and targets for cancer immunotherapy but also naturally develop cancers at similar life stages. Hence, treating rhesus macaques with spontaneous tumors bears enormous potential as model for human cancer immunotherapy. Material and Methods: We identified 2 female rhesus macaques, 23.6y (CRC_1) and 20.3y (CRC_2) old with naturally occurring colorectal cancer by imaging and clinical assessments. We collected a pre-treatment tumor biopsy in CRC_1 prior to treatment with 8 Gy intensity-modulated radiotherapy (IMRT) to the proximal portion of the tumor and 2 mg/kg i.v. pembrolizumab. The second candidate (CRC_2) was not tumor biopsy-eligible due to anemia and was treated with pembrolizumab alone. We collected blood and peripheral lymph nodes (LNs) pre- and on-treatment and complete tissue collection was performed at the 3w time point including tumor-adjacent mesenteric LNs. Follow-up assessments include IHC (e.g. CD3, CD20, IBA1), flow cytometry, cytokine assessment in plasma, and transcriptomics of LN and tumor samples. Results and Discussions: Imaging revealed focal thickening of the proximal colonic wall with disrupted architecture in CRC_1 and focal colonic thickening and an enlarged adjacent LN in CRC_2. Both tumors displayed mismatch repair-deficiency (MLH1 & PMS2 loss) and a drastic reduction in infiltrating CD3 cells in neoplastic areas compared to adjacent healthy colon. On treatment, tumor-associated LNs demonstrated a mild increase in CD20+ cells in the medullary sinuses of both patients and increased follicle numbers with normal follicular architecture in reference to peripheral LNs. In both patients there was an increased number of tertiary lymphoid structures (TLS) surrounding the tumors, predominately populated with CD20+ cells and with Ki67+ germinal centers, profoundly so in CRC_2. Moreover, IBA1+ cells abundantly infiltrated both tumors but showed a higher aggregation within the stromal elements of the neoplasms. A gradient of histologic differentiation was evident in CRC_1 and coincided with a reduction of TLS, IBA1+ cell abundance, and CD3+ cell infiltration in those areas which were poorly differentiated. Within the irradiated tumor of CRC_1, there were abundant apoptotic cells which stained positively with cleaved caspase 3 at the 3w time point. Circulating blood counts as preliminary peripheral read-out revealed a reduction in circulating lymphocytes in both patients beginning at 3d (CRC_1) resp. 6d (CRC_2) and a sharp increase in monocytes at 3d in unirradiated patient CRC_2. Conclusion: The immunological and tumoral response to pembrolizumab and radiotherapy matches the clinical response in humans and enables an unprecedented examination of the peripheral and local lymph node response. Citation Format: Simon Deycmar, George W. Schaaf, Brendan J. Johnson, J. Daniel Bourland, James D. Ververs, Christopher T. Whitlow, J. Mark Cline. Naturally occurring colorectal cancer in rhesus macaques as model for human cancer immunotherapy: a first report on pembrolizumab ± radiotherapy. [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 5203.

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