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Immunotherapy has emerged as a key modality in cancer treatment, yet its effectiveness varies significantly among patients, often due to the metabolic stress imposed by the tumor microenvironment. Hypoxia, a major factor in the tumor microenvironment, results from the high metabolic rate of tumor cells and inadequate vascularization, impairing immune cells’ function and potentially influencing gene expression profiles. Despite the widespread use of quantitative real-time PCR in immunological studies, to the best of our knowledge, data on reference gene stability in human peripheral blood mononuclear cells under hypoxic conditions is limited. In our study, we assessed the expression stability of commonly used reference genes (S18, HPRT, IPO8, RPL13A, SDHA, PPIA, and UBE2D2) in both non-stimulated and CD3/CD28-activated peripheral blood mononuclear cells cultured under normoxic, hypoxic (1% O2), and chemically induced hypoxic conditions for 24 h. Analysis using four different algorithms—delta Ct, geNorm, NormFinder, and BestKeeper—identified RPL13A, S18, and SDHA as the most suitable reference genes for human peripheral blood mononuclear cells under hypoxic conditions. In contrast, IPO8 and PPIA were found to be the least suitable housekeeping genes. The study provides essential insights into the stability of reference genes in peripheral blood mononuclear cells under hypoxic conditions, a critical but understudied aspect of immunological research. Given the significant impact of hypoxia on T cell metabolism and function in the tumor microenvironment, selecting reliable reference genes is crucial for accurate gene expression analysis. Our findings will be valuable for future studies investigating hypoxia-driven metabolic reprogramming in immune cells, ultimately contributing to a better understanding of T cell responses in cancer immunotherapy.

Dickeya solani is one of the most important pectinolytic phytopathogens responsible for high losses in potato, especially in seed potato production in Europe. Lytic bacteriophages can affect the structure of the host population and may influence spread, survival and virulence of the pathogen and in consequence, infection of the plant. In this study, we aimed to acquire information on the viability of the broad host lytic bacteriophage ΦD5 on potato, as well as to apprehend the specific effect of this bacteriophage on its host D. solani type-strain in different settings, as a preliminary step to target co-adaptation of phages and host bacteria in plant environment. Viability of the ΦD5 phage in tuber extract, on tuber surface, in potting compost, in rainwater and on the leaf surface, as well as the effect of copper sulfate, were examined under laboratory conditions. Also, the interaction of ΦD5 with the target host D. solani in vitro and in compost-grown potato plants was evaluated. ΦD5 remained infectious in potato tuber extract and rain water for up to 72 h but was inactivated in solutions containing 50 mM of copper. The phage population was stable for up to 28 days on potato tuber surface and in potting compost. In both, tissue culture and compost-grown potato plants, ΦD5 reduced infection by D. solani by more than 50%. The implications of these findings are discussed.

Solid tumors pose significant therapeutic challenges due to their resistance to conventional treatments and the complexity of the tumor microenvironment. Cell-based immunotherapies offer a promising approach, enabling precise, personalized treatment through immune system modulation. This review explores several emerging cellular therapies for solid tumors, including tumor-infiltrating lymphocytes, T cell receptor-engineered T cells, CAR T cells, CAR natural killer cells, and macrophages. Tumor-infiltrating lymphocytes and their modified versions, T cell receptor-engineered T cells and CAR T cells, provide personalized immune responses, although their effectiveness can be limited by factors like variation in tumor antigens and the suppressive nature of the tumor environment. Natural killer cells engineered with chimeric receptors offer safer, non-major histocompatibility complex-restricted targeting, while modified macrophages exploit their natural ability to enter tumors and reshape the immune landscape. CAR-modified macrophages and macrophages conjugated with drugs are also considered as therapy for solid tumors. The review also examines the implications of autologous versus allogeneic cell sources. Autologous therapies ensure immunologic compatibility but are limited by scalability and manufacturing constraints. Allogeneic approaches offer “off-the-shelf” potential but require gene editing to avoid immune rejection. Integrating synthetic biology, gene editing, and combinatorial strategies will be essential to enhance efficacy and expand the clinical utility of cellular immunotherapies for solid tumors.

Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed.

Pectobacterium parmentieri (former Pectobacterium wasabiae) is an emerging pectinolytic bacterial pathogen causing losses in potato (Solanum tuberosum L.) worldwide. Until now, there are no effective measures to protect crops from infections caused by P. parmentieri. Likewise, little is known about lytic bacteriophages that can infect and kill P. parmentieri, and that could be used in the (bio)control of this pathogen in agricultural applications. A novel lytic bacteriophage vB_Ppp_A38 (ϕA38), belonging to the order Caudovirales, was isolated and characterised in our previous studies. This report provides information about its complete genome sequence and accompanying phylogenomics. The genome of vB_Ppp_A38 consists of 75,764-bp-length, linear, double-stranded DNA with an average GC content of 48.7% and is predicted to have 97 open reading frames (ORFs), with an average length of 732 nucleotides. The open reading frames were classified into functional groups, including structural units, packing, DNA metabolism, regulation and additional (miscellaneous) functions. Comparative genomic analyses based on the whole-genome sequence indicated that the phage vB_Ppp_A38 is most similar to N4-like viruses of the family Schitoviridae, genus Cbunavirus, sharing more than 90% identity with the phages vB_PatP_CB1, vB_PatP_CB3 and vB_PatP_CB4 infecting P. atrosepticum. The bacteriophage vB_Ppp_A38 is the first Cbunavirus bacteriophage infecting other Pectobacterium spp. hosts than P. atrosepticum. As vB_Ppp_A38 is a lytic virus able to kill plant-pathogenic P. parmentieri, it can be used in the biological control of this pathogen in agricultural applications.

Lytic bacteriophages able to infect and kill Dickeya spp. can be readily isolated from virtually all Dickeya spp. containing environments, yet little is known about the selective pressure those viruses exert on their hosts. Two spontaneous D. solani IPO 2222 mutants (0.8% of all obtained mutants), DsR34 and DsR207, resistant to infection caused by lytic phage vB_Dsol_D5 (ΦD5) were identified in this study that expressed a reduced ability to macerate potato tuber tissues compared to the wild-type, phage-susceptible D. solani IPO 2222 strain. Genome sequencing revealed that genes encoding: secretion protein HlyD (in mutant DsR34) and elongation factor Tu (EF-Tu) (in mutant DsR207) were altered in these strains. These mutations impacted the DsR34 and DsR207 proteomes. Features essential for the ecological success of these mutants in a plant environment, including their ability to use various carbon and nitrogen sources, production of plant cell wall degrading enzymes, ability to form biofilms, siderophore production, swimming and swarming motility and virulence in planta were assessed. Compared to the wild-type strain, D. solani IPO 2222, mutants DsR34 and DsR207 had a reduced ability to macerate chicory leaves and to colonize and cause symptoms in growing potato plants.

Dickeya solani is one of the most important pectinolytic phytopathogens responsible for high losses in potato, especially in seed potato production in Europe. Lytic bacteriophages can affect the structure of the host population and may influence spread, survival and virulence of the pathogen and in consequence, infection of the plant. In this study, we aimed to acquire information on the viability of the broad host lytic bacteriophage [PHI]D5 on potato, as well as to apprehend the specific effect of this bacteriophage on its host D. solani type-strain in different settings, as a preliminary step to target co-adaptation of phages and host bacteria in plant environment. Viability of the [PHI]D5 phage in tuber extract, on tuber surface, in potting compost, in rainwater and on the leaf surface, as well as the effect of copper sulfate, were examined under laboratory conditions. Also, the interaction of [PHI]D5 with the target host D. solani in vitro and in compost-grown potato plants was evaluated. [PHI]D5 remained infectious in potato tuber extract and rain water for up to 72 h but was inactivated in solutions containing 50 mM of copper. The phage population was stable for up to 28 days on potato tuber surface and in potting compost. In both, tissue culture and compost-grown potato plants, [PHI]D5 reduced infection by D. solani by more than 50%. The implications of these findings are discussed.

Dickeya solani is one of the most important pectinolytic phytopathogens responsible for high losses in potato, especially in seed potato production in Europe. Lytic bacteriophages can affect the structure of the host population and may influence spread, survival and virulence of the pathogen and in consequence, infection of the plant. In this study, we aimed to acquire information on the viability of the broad host lytic bacteriophage [PHI]D5 on potato, as well as to apprehend the specific effect of this bacteriophage on its host D. solani type-strain in different settings, as a preliminary step to target co-adaptation of phages and host bacteria in plant environment. Viability of the [PHI]D5 phage in tuber extract, on tuber surface, in potting compost, in rainwater and on the leaf surface, as well as the effect of copper sulfate, were examined under laboratory conditions. Also, the interaction of [PHI]D5 with the target host D. solani in vitro and in compost-grown potato plants was evaluated. [PHI]D5 remained infectious in potato tuber extract and rain water for up to 72 h but was inactivated in solutions containing 50 mM of copper. The phage population was stable for up to 28 days on potato tuber surface and in potting compost. In both, tissue culture and compost-grown potato plants, [PHI]D5 reduced infection by D. solani by more than 50%. The implications of these findings are discussed.

In 2024, the United States was projected to experience 2 million new cancer diagnoses and approximately 611,720 cancer-related deaths, reflecting a broader global trend in which cancer cases are anticipated to exceed 35 million by 2050. This increasing burden highlights ongoing challenges in cancer treatment despite significant advances that have reduced cancer mortality by 31% since 1991. Key obstacles include the disease’s inherent heterogeneity and complexity, such as treatment resistance, cancer stem cells, and the multifaceted tumor microenvironment (TME). The TME—comprising various tumor and immune cells, blood vessels, and biochemical factors—plays a crucial role in tumor growth and resistance to therapies. Recent innovations in cancer treatment, particularly in the field of immuno-oncology, have leveraged insights into TME interactions. An emerging example is the FDA-approved therapy using tumor-infiltrating lymphocytes (TILs), demonstrating the potential of cell-based approaches in solid tumors. However, TIL therapy is just one of many strategies being explored. This review provides a comprehensive overview of the emerging field of immuno-oncology, focusing on how novel therapies targeting or harnessing components of the TME could enhance treatment efficacy and address persistent challenges in cancer care.

Treatment of solid tumors remains challenging and therapeutic strategies require continuous development. Tumor-infiltrating macrophages play a pivotal role in tumor dynamics. Here, we present a Macrophage-Drug Conjugate (MDC) platform technology that enables loading macrophages with ferritin-drug complexes. We first show that macrophages actively take up human heavy chain ferritin (HFt) in vitro via macrophage scavenger receptor 1 (MSR1). We further manifest that drug-loaded macrophages transfer ferritin to adjacent cancer cells through a process termed ‘TRAnsfer of Iron-binding protein’ (TRAIN). The TRAIN process requires direct cell-to-cell contact and an immune synapse-like structure. At last, MDCs with various anti-cancer drugs are formulated with their safety and anti-tumor efficacy validated in multiple syngeneic mice and orthotopic human tumor models via different routes of administration. Importantly, MDCs can be prepared in advance and used as thawed products, supporting their clinical applicability. This MDC approach thus represents a promising advancement in the therapeutic landscape for solid tumors. Treatment strategy of solid tumors requires continuous development. Here the authors develop a Macrophage Drug Conjugate (MDC) platform by loading ferritin-drug complexes to macrophages. MDC transfers the ferritin to cancer cells via ‘TRAnsfer of Iron binding protein’ (TRAIN) process and reduces tumor volume in various mouse tumor models.