The application of mammalian target of rapamycin inhibition (mTORi) as primary prophylactic therapy to optimize T cell effector function while preserving allograft tolerance remains challenging. Here, we present a comprehensive two-step therapeutic approach in a male patient with metastatic cutaneous squamous cell carcinoma and heart transplantation followed with concomitant longitudinal analysis of systemic immunologic changes. In the first step, calcineurin inhibitor/ mycophenolic acid is replaced by the mTORi everolimus to achieve an improved effector T cell status with increased cytotoxic activity (perforin, granzyme), enhanced proliferation (Ki67) and upregulated activation markers (CD38, CD69). In the second step, talimogene laherparepvec (T-VEC) injection further enhances effector function by switching CD4 and CD8 cells from central memory to effector memory profiles, enhancing Th1 responses, and boosting cytotoxic and proliferative activities. In addition, cytokine release (IL-6, IL-18, sCD25, CCL-2, CCL-4) is enhanced and the frequency of circulating regulatory T cells is increased. Notably, no histologic signs of allograft rejection are observed in consecutive end-myocardial biopsies. These findings provide valuable insights into the dynamics of T cell activation and differentiation and suggest that timely initiation of mTORi-based primary prophylaxis may provide a dual benefit of revitalizing T cell function while maintaining allograft tolerance.

Citation: Pagnoni A, Giroud S, Koulouri A, Hohl D, Gaide O. White globules in basal cell carcinoma: a dermoscopic sign with preoperative implications. Dermatol Pract Concept. 2021;11(1):e2021103. DOI: https://doi.org/10.5826/dpc.1101a103 Accepted: June 15, 2020; Published: January 29, 2020 Copyright: ©2021 Pagnoni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License BY-NC-4.0, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. Authorship: All authors have contributed significantly to this publication. Corresponding author: Dr. Alessandra Pagnoni, Service de Dermatologie (CHUV), Avenue de Beaumont 29, 1011 Lausanne, Switzerland. Email: alessandra.pagnoni@chuv.ch Keywords : basal cell carcinoma, MAY globules, optical coherence tomography, dermoscopy This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Julien Schaller1, Hélène Maby-El Hajjami1, Sylvie Rusakiewicz1, Kalliopi Ioannidou2, Nathalie Piazzon2, Alexandra Miles3, Déla Golshayan4, Olivier Gaide3, Daniel Hohl3, Daniel E. Speiser1 and Karin Schaeuble1 1 Department of Oncology, University Hospital Lausanne (CHUV/UNIL), Lausanne, Switzerland 2 Institute of Pathology, University Hospital Lausanne (CHUV), Lausanne, Switzerland 3 Department of Dermatology, University Hospital Lausanne (CHUV), Lausanne, Switzerland 4 Transplantation Center, University Hospital Lausanne (CHUV/UNIL), Lausanne, Switzerland Correspondence to: Karin Schaeuble, email: karin.schauble@unil.ch Keywords: lymphatic vessel; CD8+ T cell; perineural infiltration; skin squamous-cell carcinoma; tumor immunology Received: July 30, 2020 Accepted: February 26, 2021 Published: March 30, 2021 Copyright: © 2021 Schaller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy. The role of lymphatic vessels in skin squamous-cell carcinoma (sSCC), the second most common form of skin cancer, remains mostly unknown. Although anti-PD-1 therapy is beneficial for some patients with advanced sSCC, a greater understanding of disease mechanisms is still needed to develop better therapies. Using quantitative multiplex immunohistochemistry, we analyzed sSCC sections from 36 patients. CD8+ T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8+ T cell density in tumor areas. An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density. Since both, metastasis and perineural infiltration are known to affect tumor progression and patients’ prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. Our data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma. <!--x2o[ca91d152]-->