Marine Traverson

Circumstances requiring off-site learning have highlighted the lack of practical learning experience in surgery rotations. This can be particularly detrimental in understanding the concept of margins and surgical doses in oncologic surgery. This study aims to develop a high-fidelity 3D-printed model of a subcutaneous tumor that will be used to enhance clinical education of surgical oncology principles at the level of a general practitioner, from case-based clinical decision making to demarcation, excision, and inking of the margins. The model will be available for individual practical learning at home and will complement the didactic case-based modules given online during off-site clinical rotations. We hypothesized that this model would be at least as effective as a cadaver model in reinforcing the aforementioned surgical oncology principles. Initial teaching models were created in separate tissue layers using two component silicones of varying shore hardness and 3D printed molds based on computed tomography

This study addresses two important challenges related to the development of neoantigen vaccine approaches for treating T-cell lymphoma. The first is quantitative: effective vaccination must elicit anti-tumor effectors in numbers equivalent to those generated in natural infections in order to outpace cancer progression. The second challenge is the negative role that the tumor physiologic microenvironment might play in negatively regulating such immune reactivity, leading to vaccine failure. Peripheral T-cell lymphomas (PTCL) are a group of heterogeneous, clinically aggressive malignancies that are refractory to traditional chemotherapy agents and associated with a poor outcome. Survival with standardof-care CHOP therapy is <8 months.(1, 2) The persistence of a tiny population of chemoresistant malignant cells ������������������ called minimal residual disease, or MRD ������������������ demonstrable by sensitive molecular assays during treatment is thought to be the source of relapse and treatment failure. New chemotherapy agents and small molecule inhibitors have entered the picture, yet outcomes remain stubbornly inferior to those with B-cell tumors.(3, 4) Eradicating MRD via immunotherapy to improve PTCL outcomes and effect cures is a tantalizing possibility. However, trials in PTCL using monoclonal antibodies (Abs) or chimeric antigen receptor T cells targeting various T-cell surface markers have only had limited successes.(5) In solid tumors, immune checkpoint blockade has been shown to elicit T-cell responses directed against tumor-specific neoantigens, which can exert clinically meaningful effects.(6) Recently, neoantigen vaccination in melanoma has also been shown to be an effective, direct means to raise such anti-tumor immune responses.(7, 8) In spite of the strong rationale and some success in treating solid tumors, though, targeting neoantigens to eradicate MRD in PTCL is not well-explored. As non-germline-encoded proteins, neoantigens are attractive mmunotherapy targets because the corresponding (cognate) T-cell repertoire has not been subject to central deletional tolerance, and high-avidity (strongly reactive) effectors are recruitable. Despite this advantage, clinical responses to immune checkpoint blockade are not universal, and success rates vary. In fact, for most tumor types, responding patients are the minority. One mechanism underlying these differential responses is neoantigen availability, which reflects the somatic mutation rate of the tumor; lymphomas, for example, usually have few mutations and are immunologically ����������������cold���������������. Another important cause for the failure of neoantigen-targeted immunotherapy is that T cells in the tumor physiologic microenvironment must operate under harsh, unfavorable conditions, characterized by hypoxia, acidosis and lactate accumulation, which can inhibit effector functions.(9, 10). In PTCL, the situation is potentially more dire, since malignant lymphocytes occupy secondary lymphoid tissues, competing for and depleting nutrients needed by anti-tumor T cells for optimal activation and proliferation.(11) Robust antigen-driven T-cell expansion is vital for effective immunity, and increasingly, it������������������s been recognized that T-cell quantity, not just quality, is a critical determinant of the success or failure of cancer vaccines. Objective responses against tumors are only produced with a massive expansion of the cognate T-cell population to levels rivaling those achieved in viral infections. Characterizing the lymphoid microenvironment in PTCL to determine its ability to support the high metabolic demands of such T-cell proliferation is essential for developing effective strategies for neoantigen vaccination. Our preliminary data examining MRD in canine PTCL, a model of human PTCL, shows that patients always have readily detectable circulating cancer clones, despite induction of complete remission (CR). Our hypothesis is that these malignant cells, trafficking through and proliferating in lymph nodes, continue to cause significant metabolic derangements hostile to T-cell responses to vaccinat