Background: Classical Hodgkin lymphoma (cHL) is a unique lymphoid malignancy with a tumor microenvironment (TME) consisting of a small number of neoplastic—Hodgkin and Reed‐Sternberg (H‐RS) cells (<1%), surrounded by a large number of nonneoplastic infiltrating immune cells (>90%). The TME of cHL critically depends on immune cells to support tumor growth as H‐RS cells cannot survive and proliferate in isolation. Recent Findings: Programmed cell death protein 1 (PD‐1) ligand expressed on H‐RS cells inhibits the clearance of tumor by causing T‐cell exhaustion. Nivolumab and pembrolizumab, PD‐1 inhibitors, have been proven to be effective in treating adult and pediatric patients with R/R cHL. Tumor‐associated macrophages (TAMs) are a central component of TME and are known to cause poor prognosis in adult HL. However, the prognostic impact of CD68+ TAMs in pediatric HL remains ambiguous. EBV modulates the tumor milieu of HL and plays a strategic role in immune escape by enrichment of the TME with Treg cells and associated immunosuppressive cytokines in adult HL. In contrast, EBV+ pediatric patients have increased infiltration of CD8+ T‐cells and show a better therapeutic response suggesting viral‐related TME is distinct in childhood HL. The role of CASP3 in apoptosis of H‐RS cells and its correlation with response prediction in adult and pediatric HL suggest it may serve as a potential biomarker. In cHL, CD30, EBV, and NF‐κB signaling employ exosomes for cell–cell communication that triggers the migration capacity of fibroblasts, stimulate to produce proinflammatory cytokines, and help to create a tumor‐supportive microenvironment. Conclusion: The cHL microenvironment is distinct in adult and pediatric HL. Future studies are required to understand the role of interplay between H‐RS cells and EBV‐associated microenvironment and their clinical outcome. They may present novel therapeutic targets for the development of antilymphoma therapy.

BackgroundWe have previously shown that human defensin 5 (HD5) promotes HIV infectivity in both primary CD4+ T cells and HeLa cells expressing CD4 and CCR5. HD5 is induced in response to sexually transmitted infections (STIs) such as Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in STI-mediated enhancement of HIV transmission. In contrast to our findings, a recent study reports that HD5 has an anti-HIV effect in primary CD4+ T cells under serum-deprived conditions. To resolve these apparently contradictory observations, we investigated experimental parameters that might contribute to contrasting effects of HD5.ResultsSerum-deprived culture conditions were associated with anti-HIV activity. In contrast to the dependence of the HIV enhancing effect on HD5 structure, the anti-HIV activity in serum-deprived primary CD4+ T cells was independent of HD5 structure as the linear peptide [Abu] HD5 exhibited similar anti-HIV activity. Under serum deprived conditions, HD5 blocked CD4-receptor-independent HIV-1vsv infection before or after viral entry. We found that HD5 and its linear form induced significant cell death in primary CD4+ T cells under serum-deprived culture conditions. HD5-mediated apoptosis was observed as early as 2 h after addition of defensins to serum-deprived primary CD4+ T cells. In contrast to primary CD4+ T cells, HD5 did not induce cytotoxicity and promote HIV infectivity of HeLa-CD4-CCR5 cells under serum-deprived conditions.ConclusionsThese results indicate that under serum-deprived culture conditions HD5 is toxic for primary CD4+ T cells, warranting caution in data interpretation.

Adult stem cells represent a potential source for cellular therapy to treat serious human diseases. We characterized the insulin-producing cells from adult peripheral blood (designated PB-IPC), which displayed a unique phenotype. Mitochondria are normally located in the cellular cytoplasm, where they generate ATP to power the cell’s functions. Ex vivo and in vivo functional studies established that treatment with platelet-derived mitochondria can reprogram the transformation of adult PB-IPC into functional CD34+ hematopoietic stem cells (HSC)-like cells, leading to the production of blood cells such as T cells, B cells, monocytes/macrophages, granulocytes, red blood cells, and megakaryocytes (MKs)/platelets. These findings revealed a novel function of mitochondria in directly contributing to cellular reprogramming, thus overcoming the limitations and safety concerns of using conventional technologies to reprogram embryonic stem (ES) and induced pluripotent stem (iPS) cells in regenerative medicine.