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Simple Summary: Exploring the impact of heat shock protein (HSP) inhibition in cancer may give new insights into the cellular processes that these molecules sustain to promote cancer survival and may accelerate the discovery of more HSP inhibitors to be introduced in clinical trials. In this study, we explored the expression and role of high-molecular-weight HSP110 in the survival of Primary Effusion Lymphoma (PEL) cells. We found that the proper expression of this HSP is required to prevent lysosomal permeabilization, DNA damage, c-Myc downregulation and STAT3 de-phosphorylation. Indeed, HSP silencing strongly reduces PEL cell survival through the dysregulation of these processes that have been found to be interconnected. Heat shock proteins (HSPs) are highly expressed in cancer cells and represent a promising target in anti-cancer therapy. In this study, we investigated for the first time the expression of high-molecular-weight HSP110, belonging to the HSP70 family of proteins, in Primary Effusion Lymphoma (PEL) and explored its role in their survival. This is a rare lymphoma associated with KSHV, for which an effective therapy remains to be discovered. The results obtained from this study suggest that targeting HSP110 could be a very promising strategy against PEL, as its silencing induced lysosomal membrane permeabilization, the cleavage of BID, caspase 8 activation, downregulated c-Myc, and strongly impaired the HR and NHEJ DNA repair pathways, leading to apoptotic cell death. Since chemical inhibitors of this HSP are not commercially available yet, this study encourages a more intense search in this direction in order to discover a new potential treatment that is effective against this and likely other B cell lymphomas that are known to overexpress HSP110. [ABSTRACT FROM AUTHOR]

Simple Summary: Since the beginning of the COVID-19 outbreak, Cancer Centers adopted specific procedures to protect patients as well as to monitor the possible spread of SARS-CoV-2 among healthcare personnel. In April 2020, we implemented a prospective longitudinal study aimed at monitoring the serological response to SARS-Cov-2 in the healthcare personnel of a Comprehensive Cancer Center identified by the Lombardy region (the Italian region most affected by the COVID-19 pandemic) as one of the three oncologic hubs where the Regional Health Authorities referred all the cancer patients in the region. We identified a fraction of healthcare personnel with long-term anti-SARS-CoV-2 antibody response, though negative for viral RNA, who could safely approach fragile cancer patients. Since the beginning of the COVID-19 outbreak, Cancer Centers adopted specific procedures both to protect patients and to monitor the possible spread of SARS-CoV-2 among healthcare personnel (HCP). In April 2020 at Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, one of the three oncologic hubs in Lombardy where the Health Regional Authorities referred all the cancer patients of the region, we implemented a prospective longitudinal study aimed at monitoring the serological response to SARS-Cov-2 in HCP. One hundred and ten HCP answered a questionnaire and were screened by nasopharyngeal swabs as well as for IgM/IgG levels; seropositive HCPs were further screened every 40–45 days using SARS-CoV-2-specific serology. We identified a fraction of HCP with long-term anti-SARS-CoV-2 antibody responses, though negative for viral RNA, and thus probably able to safely approach fragile cancer patients. Monitoring asymptomatic HCP might provide useful information to organize the healthcare service in a Cancer Center, while waiting for the effectiveness of the active immunization by SARS-CoV-2 vaccines, which will provide protection from infection. [ABSTRACT FROM AUTHOR]