Large Numbers Of Dendritic Cells Research Articles

Antigen-loaded flagellate bacteria for enhanced adaptive immune response by intradermal injection

Since the skin limits the distribution of intradermal vaccines, a large number of dendritic cells in the skin cannot be fully utilized to elicit a more effective immune response. Here, we loaded the antigen to the surface of the flagellate bacteria that was modified by cationic polymer, thus creating antigen-loaded flagellate bacteria (denoted as ‘FB-Ag’) to overcome the skin barrier and perform the active delivery of antigen in the skin. The FB-Ag showed fast speed (∼0.2 μm s−1) and strong dendritic cell activation capabilities in the skin model in vitro. In vivo, the FB-Ag promoted the spread of antigen in the skin through active movement, increased the contact between Intradermal dendritic cells and antigen, and effectively activated the internal dendritic cells in the skin. In a mouse of pulmonary metastatic melanoma and in mice bearing subcutaneous melanoma tumor, the FB-Ag effectively increased antigen-specific therapeutic efficacy and produced long-lasting immune memory. More importantly, the FB-Ag also enhanced the level of COVID-19 specific antibodies in the serum and the number of memory B cells in the spleen of mice. The movement of antigen-loaded flagellate bacteria to overcome intradermal constraints may enhance the activation of intradermal dendritic cells, providing new ideas for developing intradermal vaccines.

Bio-adhesive Macroporous Hydrogels for In Situ Recruitment and Modulation of Dendritic Cells.

Biomaterials that enable in situ recruitment and modulation of immune cells have demonstrated tremendous promise for developing potent cancer immunotherapy such as therapeutic cancer vaccine. One challenge related to biomaterial scaffold-based cancer vaccines is the development of macroporous materials that are biocompatible and stable, enable controlled release of chemokines to actively recruit a large number of dendritic cells (DCs), contain macropores that are large enough to home the recruited DCs, and support the survival and proliferation of DCs. Bio-adhesive macroporous gelatin hydrogels were synthesized and characterized for mechanical properties, porous structure, and adhesion towards tissues. The recruitment of immune cells including DCs to chemokine-loaded bioadhesive macroporous gels was analyzed. The ability of gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor extracellular vesicles (EVs) to elicit tumor-specific CD8+ T cell responses was also analyzed. Here we develop a bioadhesive macroporous hydrogel that can strongly adhere to tissues, contain macropores that are large enough to home immune cells, are mechanically tough, and enable controlled release of chemokines to recruit and modulate immune cells in situ. The macroporous hydrogel is composed of a double crosslinked network of gelatin and polyacrylic acid, and the macropores are introduced via cryo-polymerization. By incorporating GM-CSF and tumor EVs into the macroporous hydrogel, a high number of DCs can be recruited in situ to process and present EV-encased antigens. These tumor antigen-presenting DCs can then traffic to lymphatic tissues to prime antigen-specific CD8+ T cells. This bioadhesive macroporous hydrogel system provides a new platform for in situ recruitment and modulation of DCs and the development of enhanced immunotherapies including tumor EV vaccines. We also envision the promise of this material system for drug delivery, tissue regeneration, long-term immunosuppression, and many other applications. The online version contains supplementary material available at 10.1007/s12195-023-00770-2.

Simplified Approaches for the Production of Monocyte-Derived Dendritic Cells and Study of Antigen Presentation in Bovine.

Dendritic cells are sentinels of the immune system responsible for the initiation of adaptive immune mechanisms. In that respect, the study of these cells is essential for a full understanding of host response to infectious agents and vaccines. In ruminants, the large blood volume facilitates the isolation of abundant monocytes and their derivation to other antigen-presenting cells such as dendritic cells and macrophages. However, the available protocols for the production of bovine monocyte-derived dendritic cells (moDCs) rely mostly on time-consuming and costly techniques such as density gradient centrifugation and magnetic sorting of cells. In this study, we describe a simplified protocol for the production of bovine moDC using conventional and serum-free media. We also employ moDC produced by this approach to carry out a flow cytometry-based antigen presentation assay adapted to blood fresh or frozen cells. The experimental strategies described here might enable the setup of studies involving a large number of individuals, requiring a large number of dendritic cells, or relying on the utilization of cryopreserved blood cells. These simplified protocols might contribute to the elucidation of cell-mediated immune responses in bovine.

Rapid Production of Physiologic Dendritic Cells (phDC) for Immunotherapy.

Generation of large numbers of dendritic cells (DC) for research or immunotherapeutic purposes typically involves in vitro conversion of murine bone marrow precursors or humanblood monocytes to DC via cultivation with supraphysiologic concentrations of cytokines such as GM-CSF and IL-4 for up to 7days. Alternatively, our group has recently established a new approach, based on the underlying mechanism of action of a widely used cancer immunotherapy termed Extracorporeal Photochemotherapy (ECP). Our method of rapid and cytokine-free production of therapeutically relevant DC populations,leveragingthe innate physiologic programs likely responsible for DC differentiation from blood monocytes in vivo, potentially offers a novel, inexpensive, and easily accessiblesource of DC for clinical and research uses. This approach involves ex vivo physiologic reprogramming of blood monocytes to immunologically tunable dendritic antigen-presenting cells, which we term "phDC," for physiological DC. To facilitate access and utilization of these new DC populations by the research community, in this chapter, we describethe use of a scaled-down version of the clinical ECP leukocyte-treatment devicetermed the Transimmunization (TI) chamberor plate, suitable for processing both mouse and human samples. We highlight the methodological sequences necessary to isolate mouse or human peripheral blood mononuclear cell (PBMC) from whole blood, and to expose those PBMC to the TI chamber for facilitating monocyte activation and conversion to physiological DC (phDC) through interaction with blood proteins and activated platelets under controlled flow conditions. We thenprovide sample protocols for potential applications of the generated DC, including their use as vaccinating antigen-presenting cells (APC) in murine in vivo antitumor models, and in human ex vivo T-cell stimulation and antigen cross-presentation assays which mimic clinical vaccination. We additionally highlight the technical aspects of loading mouse or human phDC with tumor-associated antigens (TAA) in the form of peptides or apoptotic tumor cells. We provide a simple and clinically relevant means to reprogram blood monocytes into functional APC, potentially replacing the comparatively expensive and clinically disappointing cytokine-derived DC which have previously dominated the dendritic cell landscape.

A method for the generation of large numbers of dendritic cells from CD34+ hematopoietic stem cells from cord blood

Dendritic cells (DCs) play a central role in regulating innate and adaptive immune responses. It is well accepted that their regulatory functions change over the life course. In order to study DCs function during early life it is important to characterize the function of neonatal DCs. However, the availability of neonatal DCs is limited due to ethical reasons or relative small samples of cord blood making it difficult to perform large-scale experiments. Our aim was to establish a robust protocol for the generation of neonatal DCs from cord blood derived CD34+ hematopoietic stem cells. For the expansion of DC precursor cells we used a cytokine cocktail containing Flt-3 L, SCF, TPO, IL-3 and IL-6. The presence of IL-3 and IL-6 in the first 2 weeks of expansion culture was essential for the proliferation of DC precursor cells expressing CD14. After 4 weeks in culture, CD14+ precursor cells were selected and functional DCs were generated in the presence of GM-CSF and IL-4. Neonatal DCs were then stimulated with Poly(I:C) and LPS to mimic viral or bacterial infections, respectively. Poly(I:C) induced a higher expression of the maturation markers CD80, CD86 and CD40 compared to LPS. In line with literature data using cord blood DCs, our Poly(I:C) matured neonatal DCs cells showed a higher release of IL-12p70 compared to LPS matured neonatal DCs. Additionally, we demonstrated a higher release of IFN-γ, TNF-α, IL-1β and IL-6, but lower release of IL-10 in Poly(I:C) matured compared to LPS matured neonatal DCs derived from cord blood CD34+ hematopoietic stem cells. In summary, we established a robust protocol for the generation of large numbers of functional neonatal DCs. In line with previous studies, we showed that neonatal DCs generated form CD34+ cord blood progenitors have a higher inflammatory potential when exposed to viral than bacterial related stimuli.

Abstract B045: Antigen-free cancer vaccine to treat poorly immunogenic tumors

Abstract Certain chemotherapeutic drugs can elicit immunogenic death of tumor cells and enhance antitumor immune responses. Here we explore whether immunogenic chemotherapy can be utilized for the development of antigen-free cancer vaccines, by combining it with peritumorally injected biomaterial scaffolds that recruit dendritic cells (DCs) for subsequent antigen presentation and T-cell priming. Pore-forming alginate gels containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and a doxorubicin-iRGD conjugate were found to efficiently induce the apoptosis of 4T1 triple-negative breast cancer cells in vivo, while recruiting large numbers of DCs. The co-encapsulation of CpG oligodeoxynucleotides in the gel significantly enhanced the immunogenic death of 4T1 cells, increased systemic tumor-specific CD8+ T-cells and tumoral infiltration of CD8+ T-cells, repolarized tumor-associated macrophages towards an inflammatory M1-like phenotype, and resulted in significantly improved antitumor efficacy. This in situ antigen-free gel vaccine shows promise for the treatment of poorly immunogenic tumors, and more broadly, may serve as a facile platform to enable in situ personalized cancer vaccination without requiring identification of tumor-specific antigens and manufacturing of personalized vaccines. Citation Format: Miguel C. Sobral, Hua Wang, Alexander J. Najibi, Aileen Li, Catia S. Verbeke, David J. Mooney. Antigen-free cancer vaccine to treat poorly immunogenic tumors [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B045.

Bone Marrow-Derived Dendritic Cells.

Dendritic cells are a specialized type of antigen-presenting cell that bridges both innate and adaptive immune system function. While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. The isolation and culture of dendritic cells from mouse tissues can be challenging, due in part to the low number of cells isolated. The following protocol outlines methods to optimize the isolation and culture of large numbers of dendritic cells from mouse bone marrow to facilitate a broad range of downstream experimental applications.

Characteristics of New Onset Herpes Simplex Keratitis after Keratoplasty.

Purpose To observe clinical characteristics and treatment outcomes of new onset herpes simplex keratitis (HSK) after keratoplasty. Methods Among 1,443 patients (1,443 eyes) who underwent keratoplasty (excluding cases of primary HSK) in Shandong Eye Hospital, 17 patients suffered postoperative HSK. The clinical manifestations, treatment regimens, and prognoses of the patients were evaluated. Results The incidence of new onset HSK after keratoplasty was 1.18%. Epithelial HSK occurred in 10 eyes, with dendritic epithelial infiltration in 6 eyes and map-like epithelial defects in 4 eyes. Nine eyes had lesions at the junction of the graft and recipient. Stromal necrotic and endothelial HSK occurred in 7 eyes, presenting map-shaped ulcers in the entire corneal graft and recipient (two eyes) or at the graft-recipient junction (five eyes). Confocal microscopy revealed infiltration of a large number of dendritic cells at the junction of the lesion and transparent cornea. All 10 eyes with epithelial lesions and two eyes suffering stromal lesions of ≤1/3 corneal thickness healed after systematic and local antiviral treatment. Best-corrected visual acuity and corneal graft transparency were restored. For stromal HSK with an ulcer of >1/3 corneal thickness, amniotic membrane transplantation was performed, and visual acuity and graft transparency decreased significantly. Conclusion New onset HSK after keratoplasty primarily resulted in epithelial and stromal lesion, involving both the graft and recipient. Effective treatments included antiviral medications and amniotic membrane transplantation. Delayed treatment may lead to aggravated graft opacification.

Microenvironmental Control of High-Speed Interstitial T Cell Migration in the Lymph Node

T cells are highly concentrated in the lymph node (LN) paracortex, which serves an important role in triggering adoptive immune responses. Live imaging using two-photon laser scanning microscopy revealed vigorous and non-directional T cell migration within this area at average velocity of more than 10 μm/min. Active interstitial T cell movement is considered to be crucial for scanning large numbers of dendritic cells (DCs) to find rare cognate antigens. However, the mechanism by which T cells achieve such high-speed movement in a densely packed, dynamic tissue environment is not fully understood. Several new findings suggest that fibroblastic reticular cells (FRCs) and DCs control T cell movement in a multilateral manner. Chemokines and lysophosphatidic acid produced by FRCs cooperatively promote the migration, while DCs facilitate LFA-1-dependent motility via expression of ICAM-1. Furthermore, the highly dense and confined microenvironment likely plays a key role in anchorage-independent motility. We propose that T cells dynamically switch between two motility modes; anchorage-dependent and -independent manners. Unique tissue microenvironment and characteristic migration modality of T cells cooperatively generate high-speed interstitial movement in the LN.

Modified lamellar keratoplasty and immunosuppressive therapy guided by in vivo confocal microscopy for perforated Mooren's ulcer

AimTo observe the efficacy of modified lamellar keratoplasty (LK) and immunosuppressive therapy guided by in vivo confocal microscopy (IVCM) for perforated Mooren's ulcer.Methods25 patients (31 eyes) with perforated Mooren's ulcer...

Dendritic Cells Loaded With mRNA Encoding Full-length Tumor Antigens Prime CD4+ and CD8+ T Cells in Melanoma Patients

It is generally thought that dendritic cells (DCs) loaded with full-length tumor antigen could improve immunotherapy by stimulating broad T-cell responses and by allowing treatment irrespective of the patient's human leukocyte antigen (HLA) type. To investigate this, we determined the specificity of T cells from melanoma patients treated with DCs loaded with mRNA encoding a full-length tumor antigen fused to a signal peptide and an HLA class II sorting signal, allowing presentation in HLA class I and II. In delayed-type hypersensitive (DTH)-biopsies and blood, we found functional CD8(+) and CD4(+) T cells recognizing novel treatment-antigen-derived epitopes, presented by several HLA types. Additionally, we identified a CD8(+) response specific for the signal peptide incorporated to elicit presentation by HLA class II and a CD4(+) response specific for the fusion region of the signal peptide and one of the antigens. This demonstrates that the fusion proteins contain newly created immunogenic sequences and provides evidence that ex vivo-generated mRNA-modified DCs can induce effector CD8(+) and CD4(+) T cells from the naive T-cell repertoire of melanoma patients. Thus, this work provides definitive proof that DCs presenting the full antigenic spectrum of tumor antigens can induce T cells specific for novel epitopes and can be administered to patients irrespective of their HLA type.

Dendritic Cells of Synovium in Experimental Model of Osteoarthritis of Rabbits

Aims: Dendritic cells (DCs) are critical initiators of immune responses, however, its distribution and role in osteoarthritis (OA) remains largely unknown. This study is to investigate the distribution of DCs in the rabbits’ synovium of experimental OA. Methods: Model of OA was established by excising the medial meniscus of both hind knees in New Zealand white rabbits. The grades of synovium and articular cartilage were assessed and scored by hematoxylin eosin stain after 2, 4, 8, and 12 weeks of operation. The distribution of DCs was investigated by immunohistochemistry staining in the synovium from OA rabbits. The levels of IL-1β and TNF-α in synovial fluid were measured by ELISA kits. Results: Molecular markers for DCs, such as DC-LAMP, CD80, CD83, and CD86 were detected in lymphoid aggregations and perivenular infiltration areas in the synovium from OA rabbits. Large numbers of DCs were observed in the synovium in the early stages (2 or 4 weeks) after operation. The number of DCs was significantly increased with the progression of inflammatory grade in synovium in the same early stages. Expression of IL-1β and TNF-α were also increased in the early stages, then decreased with the inflammatory regression in synovium. Conclusion: The data from this study strongly suggested that DCs may play a key role, at least in part, in inflammation of the OA pathogenesis, especially in the early stages of OA.

New Hepatitis B Vaccine Schedule for Children with Celiac Disease

Dear Editor, The article by Ertekin et al. published in Hepatitis Monthly indicates that a new hepatitis B virus (HBV) vaccine schedule should be created for children with celiac disease (CD), and the response of all children with CD to the HBV vaccine should be routinely investigated [1]. The authors investigated a group of children with CD vaccinated against HBV and found that the anti-HBs titer was not detected in a significant percentage (38.5%) of children. In addition, the clinical presentation of the disease and dietary compliance of the patients seemed to play a role in nonresponsiveness to the HBV vaccine. Therefore, the authors suggest a different immunization schedule. Most studies indicate that major histocompatibility complex (MHC) and human leukocyte II antigens (HLA-II) are responsible for nonresponsiveness to HBV vaccine [2][3][4][5]. However, Nemes et al. [6] found that the percentage of seroconversion (95.5%) in a group of patients vaccinated after initiating dietary treatment was similar to that in healthy individuals, and overall, 36 out of 37 nonresponders consuming a controlled gluten-free diet showed seroconversion after administering a booster dose of vaccine. This finding shows that HLA DQ alleles do not have a primary role in nonresponsiveness to HBV vaccine. The nature of protection afforded by vaccination is complex and, although both humoral and cytotoxic T-cell responses play a role, long-term protection is dependent upon immunological memory. The general belief is that immunological memory persists for a long period after natural infection and administration of live vaccines. For many years, the response to HBV vaccination is determined by measuring the anti-HBs titer, and a patient with an anti-HBs level < 10 mIU/mL is considered to be a nonresponder. However, responsiveness to HBV vaccination is usually determined by testing within 2-6 months after receiving the third dose of the vaccine. Thus, the nonresponsiveness to HBV vaccine might be secondary to the tendency of older individuals having a weaker response to the vaccine or not developing immunity. In patients with anti-HBs level < 10 IU/L, a schedule for booster vaccinations should be proposed, but no consensus has been achieved on the management of nonresponders to date. A high dose of HB vaccine is administered in healthy individuals, but this procedure is not uniformly successful [7]. Recently, 90% seroconversion was observed in a pilot study in patients after administration of a booster dose of vaccine by the intradermal (ID) route [8]. Large prospective randomized studies are required to validate this procedure to improve the efficacy and safety of the current standard protocol. The mechanism of induction of immunogenicity via intradermal administration is not clearly established but may be related to the sequestration of the antigens in the dermis for a long time after intradermal injection. The dermis contains large numbers of dendritic cells (the most potent antigen-presenting cells) that are important for the ID route of immunization, and these cells are thought to induce cell-mediated immune responses, particularly CD4+ and CD8+ T-cell responses. In addition, dendritic cells enhance antibody production by B cells through efficient induction of CD4+ T-cell modulation of B cells and thus a lower antigen dose is required to produce an immune response.

Functional Divergence among CD103+Dendritic Cell Subpopulations following Pulmonary Poxvirus Infection

A large number of dendritic cell (DC) subsets have now been identified based on the expression of a distinct array of surface markers as well as differences in functional capabilities. More recently, the concept of unique subsets has been extended to the lung, although the functional capabilities of these subsets are only beginning to be explored. Of particular interest are respiratory DCs that express CD103. These cells line the airway and act as sentinels for pathogens that enter the lung, migrating to the draining lymph node, where they add to the already complex array of DC subsets present at this site. Here we assessed the contributions of these individual populations to the generation of a CD8(+) T-cell response following respiratory infection with poxvirus. We found that CD103(+) DCs were the most effective antigen-presenting cells (APC) for naive CD8(+) T-cell activation. Surprisingly, we found no evidence that lymph node-resident or parenchymal DCs could prime virus-specific cells. The increased efficacy of CD103(+) DCs was associated with the increased presence of viral antigen as well as high levels of maturation markers. Within the CD103(+) DCs, we observed a population that expressed CD8alpha. Interestingly, cells bearing CD8alpha were less competent for T-cell activation than their CD8alpha(-) counterparts. These data show that lung-migrating CD103(+) DCs are the major contributors to CD8(+) T-cell activation following poxvirus infection. However, the functional capabilities of cells within this population differ with the expression of CD8, suggesting that CD103(+) cells may be divided further into distinct subsets.

Mast Cells Augment Adaptive Immunity by Orchestrating Dendritic Cell Trafficking through Infected Tissues

Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the serum antibody response is significantly diminished and less protective following passive immunization in a urinary tract infection (UTI) model in wild-type mice. MCs were found to recruit large numbers of dendritic cells (DCs) into the infected tissue site, which eventually migrated into draining lymph nodes (DLNs) during a prolonged time course. This pattern of trafficking was facilitated by MC-generated TNF, which increased the expression of E-selectin on local blood vessels. Antibody blockade of E-selectin inhibited DC recruitment into the site of infection and DLNs and consequently impaired the primary humoral immune response. Thus, during infection, resident MCs contribute to the primary protective adaptive response through recruitment of DCs from the circulation into infected sites.

Effects of Type I Interferons on the Adjuvant Properties of Plasmid Granulocyte-Macrophage Colony-Stimulating Factor In Vivo

While administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) can induce the local recruitment of activated antigen-presenting cells at the site of vaccine inoculation, this cellular recruitment is associated with a paradoxical decrease in local vaccine antigen expression and vaccine-elicited CD8+ T-cell responses. To clarify why this cytokine administration does not potentiate immunization, we examined the recruited cells and expressed inflammatory mediators in muscles following intramuscular administration of plasmid GM-CSF in mice. While large numbers of dendritic cells and macrophages were attracted to the site of plasmid GM-CSF inoculation, high concentrations of type I interferons were also detected in the muscles. As type I interferons have been reported to damp foreign gene expression in vivo, we examined the possibility that these local innate mediators might decrease plasmid DNA expression and therefore the immunogenicity of plasmid DNA vaccines. In fact, we found that coadministration of an anti-beta interferon monoclonal antibody with the plasmid DNA immunogen and plasmid GM-CSF restored both the local antigen expression and the CD8+ T-cell immunogenicity of the vaccine. These data demonstrate that local innate immune responses can change the ability of vaccines to generate robust adaptive immunity.

Cytokines mRNA in bone marrow-derived dendritic cells in asthmatic mouse

By inducing and amplifying dendritic cells (DCs) derived from the bone marrow of asthma murine in vitro, cytokines mRNA were expressed, and the functions of DCs were investigated. Cells isolated from murine bone marrow have been cultured with rmGM-CSF and rmIL-4, and the expression of cytokines mRNA was determined by ribonuclease protection assay combined with multi-probe templates. Large numbers of DCs have been obtained from bone marrow, and they expressed interleukin-13 (IL-13), interleukin-9 (IL-9), and interleukin-3 (IL-3) mRNA. Moreover, the level of IL-13 mRNA and IL-9 mRNA expressed by DCs in asthmatic mice was significantly higher than those in the control groups (P 0.05). DCs are very important in the forming and developing of asthma, which implies that the therapy targeted at DCs will possibly become a new goal.

The large scale generation of dendritic cells for the immunization of patients with non-small cell lung cancer (NSCLC)

In the current study, we generated large numbers of dendritic cells (DCs) from patients with non-small cell lung cancer (NSCLC) for a vaccine trial. The DCs were generated from CD14+ cells obtained by immuno-magnetic bead column separation technique. The CD14+ cells were placed in culture in the presence of granulocyte macrophage colony stimulating factor (GMCSF) and Interleukin 4 (IL-4). At Day 7, apoptotic bodies derived from an allogeneic NSCLC line 1650-TC were added to the cultures at a DC:tumor cell ratio of 1:1. At Day 8, the DCs were harvested, washed and injected intradermally into patients. Using this protocol we have prepared DCs for 16 patients. An average of 9.3 x 10(7) DCs was injected for the priming dose and 8.2 x 10(7) DCs for the boost. Clinical evaluation of the patients and immune assessment are presented in a separate report. The current report provides evidence for the large scale production of functional DCs derived from patients with NSCLC which can be used as vaccines in clinical trials.

Anatomical and cellular basis of immunity and tolerance in the intestine.

Anatomical and cellular basis of immunity and tolerance in the intestine.

Immunotherapy exploiting the versatility of dendritic cells.

Dendritic cells (DC) are the most potent antigen-presenting cells that initiate T cell-mediated immune responses. The development of methods to generate a large number of DC in vitro has facilitated their application to immunotherapy. Adding tumor antigens to DC in vitro and administering them to cancer patients is expected to induce effective immune responses to cancers, which are poorly immunogenic in most cases. There are several parameters that need to be optimized to improve the efficacy of DC-based immunotherapy. Because the immune system has developed in order to eliminate microbial pathogens and is thus well equipped with machinery for that purpose, reproducing events occurring during anti-infection immune responses for antitumor immunity may lead to the development of effective tumor immunotherapy.