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Simple Summary: Classical Hodgkin lymphoma (cHL) is a highly curable disease, with about 80% of patients cured using standard first-line chemotherapy. However, outcomes for relapsed/refractory patients remain unfavorable and there is a critical lack of predictive biomarkers for early identification of these patients who may benefit from new therapeutic strategies. Here we evaluated the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients using NanoString technology. We identified a 19-gene immune signature predictive of relapse at the time of diagnosis, which was found to be strongly dependent on histological subtype. Moreover, comparative analyses between paired diagnostic/relapsed biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, highlighting an immune contexture shift at relapse not found in mixed-cellularity cases. Overall, these results strongly suggest that the predictive value of immune signature in cHL is influenced by histological subtype, a criterion that should be considered when assessing new immunotherapy strategies. Despite the success of standard front-line chemotherapy, 20% of classical Hodgkin lymphoma (cHL) patients still relapse or have refractory disease (r/r), and a subset of them die due to disease progression. There is a critical lack of predictive factors for early identification of those r/r patients who may benefit from new therapeutic strategies. This study aimed to evaluate the dynamic expression of 586 immune-related genes in a cohort of 42 cHL patients including 30 r/r cHL after first-line chemotherapy. Gene expression profiling (GEP) using NanoString technology identified a 19-gene immune signature at diagnosis predictive of cHL relapse, but dependent on histological subtypes. Genes related to tumor survival were found upregulated while genes related to B-lineage were downregulated at diagnosis in r/r nodular sclerosis cHL. In contrast to the mixed-cellularity subtype, comparative GEP analyses between paired diagnosis/relapse biopsies of nodular sclerosis cHL showed 118 differentially expressed genes, supporting an immune contexture switch at relapse with upregulation of immunosuppressive cytokines, such as LGALS1 and TGFB1, and downregulation of the T-cell co-stimulatory receptor ICOS. These results indicate that the predictive value of immune signature in cHL is strongly influenced by histological subtype which should be considered when assessing new immunotherapy target strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: During the fight against tumor, some cells of the immune system such as cytotoxic lymphocytes eliminate tumoral cells while others such as tumor-associated macrophages favor tumor development. Mast cells (MCs) are multifaceted immune cells whose role in cancer is still poorly understood. Moreover, MCs are poorly characterized in the context of cancer and their presence in the tumor microenvironment has been reported to be either associated with good or bad prognosis. In this pilot study we characterized tumor-associated MCs (TAMCs) in lung cancer. We showed that TAMCs exhibited a typical phenotype and can be classified in two subsets according to alphaE integrin (CD103) expression. CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103− counterpart. This study revealed that a high frequency of total TAMC correlated with better overall survival and progression free survival in patients and underlined MC heterogeneity in cancer. Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). However, MCs have been only barely characterized in studies focusing on global immune infiltrate phenotyping. Consequently, their role in cancer is still poorly understood. Furthermore, their prognosis value is confusing since MCs have been associated with good and bad (or both) prognosis depending on the cancer type. In this pilot study performed on a surgical cohort of 48 patients with Non-Small Cell Lung Cancer (NSCLC), we characterized MC population within the TME and in matching non-lesional lung areas, by multicolor flow cytometry and confocal microscopy. Our results showed that tumor-associated MCs (TAMCs) harbor a distinct phenotype as compared with MCs present in non-lesional counterpart of the lung. Moreover, we found two TAMCs subsets based on the expression of CD103 (also named alphaE integrin). CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103− counterpart. In spite of these characteristics, we did not observe a prognosis advantage of a high frequency of CD103+ TAMCs, while a high frequency of total TAMC correlated with better overall survival and progression free survival. Together, this study reveals that TAMCs constitute a heterogeneous population and indicates that MC subsets should be considered for patients' stratification and management in future research. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi's sarcoma, a rare opportunistic tumor, is observed in four epidemiological conditions (AIDS-related, iatrogenic, endemic or classic KS). Although in most cases KS is an indolent disease, it can be locally aggressive and/or it can invade other organs than the skin, resulting in more severe presentations, especially in patients with severe immunosuppression. There is no consensus on the imaging workup that is necessary for either the initial staging of the disease or the follow-up. Future perspectives include the use of certain non-invasive imaging tools that may help to evaluate the clinical response to treatment, as well as certain new histological markers that may help in guiding the treatment planning for this atypical neoplasm. Kaposi's sarcoma (KS) is a rare, atypical malignancy associated with immunosuppression and can be qualified as an opportunistic tumor, which responds to immune modulation or restoration. Four different epidemiological forms have been individualized (AIDS-related, iatrogenic, endemic or classic KS). Although clinical examination is sufficient to diagnose cutaneous lesions of KS, additional explorations are necessary in order to detect lesions involving other organs. New histological markers have been developed in recent years concerning the detection of HHV-8 latent or lytic proteins in the lesions, helping to confirm the diagnosis when it is clinically doubtful. More recently, the evaluation of the local immune response has also been shown to provide some guidance in choosing the appropriate therapeutic option when necessary. We also review the indication and the results of conventional radiological imaging and of non-invasive imaging tools such as 18F-fluoro-deoxy-glucose positron emission tomography, thermography and laser Doppler imaging for the diagnosis of KS and for the follow-up of therapeutic response in patients requiring systemic treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: In most Epstein–Barr virus (EBV)-infected individuals, the virus establishes a lifelong latent infection with no specific clinical manifestation. However, EBV primary infection and secondary reactivation may cause various EBV-associated lymphoproliferative disorders (LPD), including hematologic malignancies. Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV, more commonly encountered in Asians and Latin Americans. They encompass a spectrum of disorders ranging from indolent reactive lesions to malignant and aggressive diseases. Despite novel insights from high-throughput molecular studies, the pathogenesis of these disorders is not well understood, and EBV-positive T/NK LPD diagnoses remain challenging due to their rarity and considerable overlap. Indeed, this article discusses new insights into EBV-positive T/NK LPD and focuses on diagnosis challenges, describing the difficulties to clarify the borders between overlapping LPD subtypes. Epstein–Barr virus (EBV) is a ubiquitous virus detected in up to 95% of the general population. Most people are asymptomatic, while some may develop a wide range of EBV-associated lymphoproliferative disorders (LPD). Among them, EBV-positive T/NK LPD are uncommon diseases defined by the proliferation of T- or NK-cells infected by EBV. The 2017 World Health Organization (WHO) classification recognizes the following entities characterized by different outcomes: chronic active EBV infection of T- or NK-cell types (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, EBV-positive aggressive NK-cell leukemia, extra nodal NK/T-cell lymphoma nasal type, and the new provisional entity known as primary EBV-positive nodal T/NK-cell lymphoma. In addition, EBV associated-hemophagocytic lymphohistiocytosis is part of EBV-positive T/NK LPD, but has not been included in the WHO classification due to its reactive nature. Despite novel insights from high-throughput molecular studies, EBV-positive NK/T-cell LPD diagnoses remain challenging, especially because of their rarity and overlap. Until now, an accurate EBV-positive NK/T LPD diagnosis has been based on its clinical presentation and course correlated with its histological features. This review aims to summarize clinical, pathological and molecular features of EBV-positive T/NK LPD subtypes and to provide an overview of new understandings regarding these rare disorders. [ABSTRACT FROM AUTHOR]