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Introduction: Studying diseased human tissues offers better insights into the intricate interactions between pathogens and the human host. In conditions such as HIV and cancers, where diseases primarily manifest in tissues, peripheral blood studies are limited in providing a thorough understanding of disease processes and localized immune responses. Methods: We describe a study designed to obtain excisional lymph nodes from volunteers for HIV reservoir studies. Since study commencement in 2015, 181 lymph node excisions have been performed, resulting in collection of 138 lymph node tissues. Lymph nodes were surgically excised from study volunteers using a minimally invasive procedure, performed in a minor theater under local anesthesia. Results: The surgery takes less than 30 minutes to complete, minimizing risk and stress on the volunteer. The small incision made during the procedure typically heals within a week. The associated discomfort is generally manageable, and participants are often able to resume their regular activities within a day. Only 5.5% of the study participants experienced minor adverse events, such as swelling and prolonged wound healing, recovering within 2 weeks with no serious adverse events reported. Discussion: Our study demonstrates that when done with outmost care, obtaining excised lymph nodes for research is relatively safe and practical. [ABSTRACT FROM AUTHOR]

In recent years, immunotherapy has emerged as a crucial component of cancer treatment. However, its efficacy remains limited across various cancer types, highlighting unmet needs. Poliovirus receptor-related 2 (PVRL2) and Poliovirus receptor (PVR) are members of the Nectin and Nectin-like Molecules family, known for their role as cell-cell adhesion molecules. With the development of immunotherapy, their involvement in tumor immune mechanisms as immune checkpoint factors has garnered significant attention. PVRL2 and PVR are predominantly expressed on tumor cells and antigen-presenting cells, binding to PVRIG and TIGIT, respectively, which are primarily found on T and NK cells, thereby suppressing antitumor immunity. Notably, gynecological cancers such as ovarian and endometrial cancers exhibit high expression levels of PVRL2 and PVR, with similar trends observed in various other solid and hematologic tumors. Targeting these immune checkpoint pathways offers a promising therapeutic avenue, potentially in combination with existing treatments. However, the immunomodulatory mechanism involving these bindings, known as the DNAM-1 axis, is complex, underscoring the importance of understanding it for developing novel therapies. This article comprehensively reviews the immunomodulatory mechanisms centered on PVRL2 and PVR, elucidating their implications for various cancer types. [ABSTRACT FROM AUTHOR]

The incidence of melanoma is increasing year by year and is highly malignant, with a poor prognosis. Its treatment has always attracted much attention. Among the more clinically applied immunotherapies are immune checkpoint inhibitors, bispecific antibodies, cancer vaccines, adoptive cell transfer therapy, and oncolytic virotherapy. With the continuous development of technology and trials, in addition to immune monotherapy, combinations of immunotherapy and radiotherapy have shown surprising efficacy. In this article, we review the research progress of immune monotherapy and combination therapy for advanced melanoma, with the aim of providing new ideas for the treatment strategy for advanced melanoma. [ABSTRACT FROM AUTHOR]

Acral lentiginous melanoma is a rare subtype of melanoma generally associated with poor outcomes, even when diagnosed at an early stage. The tumor genetic profile remains poorly understood, but it is known to have a suppressed immune environment compared to that of non-acral cutaneous melanomas, which limits therapy options. There is significant attention on the development of novel therapeutic approaches, although studies are limited due to disease rarity. For local disease, wide local excision remains the standard of care. Due to frequent under-staging on preoperative biopsy, wider margins and routine sentinel lymph node biopsy may be considered if morbidity would not be increased. For advanced disease, anti-PD1 monotherapy or combination therapy with anti-PD1 and anti-CTLA4 agents have been used as first-line treatment modalities. Anti-PD1 and anti-CTLA4 combination therapies have been shown to be particularly beneficial for patients with BRAF-mutant acral lentiginous melanoma. Other systemic combination regimens and targeted therapy options may be considered, although large studies with consistent results are lacking. Regional and intralesional therapies have shown promise for cutaneous melanomas, but studies generally have not reported results for specific histologic subtypes, especially for acral melanoma. Overall, the unique histologic and genetic characteristics of acral lentiginous melanoma make therapy options significantly more challenging. Furthermore, studies are limited, and data reporting has been inconsistent. However, more prospective studies are emerging, and alternative therapy pathways specific to acral lentiginous melanoma are being investigated. As further evidence is discovered, reliable treatment guidelines may be developed. [ABSTRACT FROM AUTHOR]

The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms. In order to improve current therapies and develop new ones, the immunotherapy field still has an unmet need in identifying other molecules that act as immune checkpoints, and uncovering other mechanisms that promote CBR. [ABSTRACT FROM AUTHOR]

Managing malignant brain tumors remains a significant therapeutic hurdle that necessitates further research to comprehend their treatment potential fully. Oncolytic viruses (OVs) offer many opportunities for predicting and combating tumors through several mechanisms, with both preclinical and clinical studies demonstrating potential. OV therapy has emerged as a potent and effective method with a dual mechanism. Developing innovative and effective strategies for virus transduction, coupled with immune checkpoint inhibitors or chemotherapy drugs, strengthens this new technique. Furthermore, the discovery and creation of new OVs that can seamlessly integrate gene therapy strategies, such as cytotoxic, anti-angiogenic, and immunostimulatory, are promising advancements. This review presents an overview of the latest advancements in OVs transduction for brain cancer, focusing on the safety and effectiveness of G207, G47Δ, M032, rQNestin34.5v.2, C134, DNX-2401, Ad-TD-nsIL12, NSC-CRAd-S-p7, TG6002, and PVSRIPO. These are evaluated in both preclinical and clinical models of various brain tumors., (© 2024. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.)