• breast cancer
• cervical cancer
• cholangiocarcinoma
• combination cancer treatment
• lung cancer
• photodynamic therapy

• 2023-06216 Dongduk Women's University

• DAMPs
• MHY1485
• anti-cancer immunity
• immunogenic cell death
• radiation

• Animals
• Mice
• Immunogenic Cell Death
• Carcinoma, Lewis Lung/radiotherapy
• Carcinoma, Lewis Lung/pathology
• CD8-Positive T-Lymphocytes
• Cell Line, Tumor
• Morpholines
• Triazines

• Anti-Yo autoantibodies
• Autoantibodies
• CDR2L protein
• Immune checkpoint inhibitors
• Paraneoplastic cerebellar degeneration

• Humans
• Mice
• Female
• Animals
• Paraneoplastic Cerebellar Degeneration
• Pilot Projects
• Cerebellum/pathology
• Purkinje Cells/metabolism
• Cerebellar Ataxia/pathology
• Autoantibodies

• ANR-18-RHUS-0012 Agence Nationale de la Recherche
• ANR-11-LABX-0042 Agence Nationale de la Recherche
• DQ20170336751 Fondation pour la Recherche Médicale

• cancer–immunity cycle
• clinical trial
• hepatocellular carcinoma
• immune checkpoint inhibitor
• locoregional therapy

• 23K16770 Japan Society for the Promotion of Science
• 21H02892 Japan Society for the Promotion of Science
• JP23fk0210130 Japan Agency for Medical Research and Development
• JP23fk0210090 Japan Agency for Medical Research and Development
• JP23fk0210115 Japan Agency for Medical Research and Development
• Princess Takamatsu Cancer Research Fund Princess Takamatsu Cancer Research Fund
• Daiichi Sankyo Foundation of Life Science Daiichi Sankyo Foundation of Life Science
• Takeda Science Foundation Takeda Science Foundation

• abscopal effect
• cancer
• cryoablation
• immunotherapy
• local therapy
• photodynamic therapy
• radiotherapy

• Impacting Research Innovation and Technology
• Department of Science and Technology, Ministry of Science and Technology, India

• DC vaccines
• cancer immunotherapy
• dendritic cells

• Humans
• Biocompatible Materials
• Dendritic Cells
• Drug-Related Side Effects and Adverse Reactions
• Extracellular Vesicles
• Immunogenic Cell Death

Background: Immunotherapy is changing the way we treat cancer. Immunogenic cell death (ICD) has received considerable attention in the treatments of various cancer types, due to the long-lasting antitumor responses elicited in human body. However, to date, no relevant bibliometric research has been reported.

Methods: Publications related to ICD in cancer research were collected from the Web of Science Core Collection. Using CiteSpace, VOSviewer and an online platform, the analyses of co-author, co-citation, and co-occurrence of terms retrieved from literatures were carried out.

Results: A total of 1,577 publications were included in this study. The global research literatures on ICD in cancer research have been increasing from 2005 to 2021. China, the United States and France dominated in this area and had close collaborations with many countries. Six of the top 10 most contributive institutions were from France. When it comes to author analysis, Kroemer G, Zitvogel L, Kepp O, Garg AD and Galluzzi L were in both the top 10 most productive authors and top 10 most co-cited authors lists. The co-occurring author keywords could be grouped into three clusters: “biomarkers of ICD”, “nanoparticles” and “combination therapy”. In terms of promising hotspots, keywords (author keywords and KeyWords Plus) with recent citation bursts could be summarized into two aspects: “tumor microenvironment” and “nanoparticles”.

Conclusion: Increased attention has been paid to ICD in cancer treatment. However, there are still many unresolved domains in the field of ICD, such as clinical application and molecular mechanisms of this cell death process. ICD-inducing modalities combined with nanotechnology could potentiate the current immunotherapies, and will be hotspots for future research.

• NFκB dynamics
• anti-tumor immunity
• fate decisions
• immunogenic cell death
• immunotherapy

The protocol used to induce cell death for generating vaccines from whole tumor cells is a critical consideration that impacts vaccine efficacy. Here we compared how different protocols used to induce cell death impacted protection provided by a prophylactic whole tumor cell vaccine in a mouse melanoma model. We found that melanoma cells exposed to γ-irradiation or lysis combined with UV-irradiation (LyUV) provided better protection against tumor challenge than lysis only or cells exposed to UV-irradiation. Furthermore, we found that the immunoregulatory cytokine, IL-27 enhanced protection against tumor growth in a dose-dependent manner when combined with either LyUV or γ-irradiated whole tumor cell vaccine preparations. Taken together, this data supports the use of LyUV as a potential protocol for developing whole tumor cell prophylactic cancer vaccines. We also showed that IL-27 can be used at low doses as a potent adjuvant in combination with LyUV or γ-irradiation treated cancer cells to improve the protection provided by a prophylactic cancer vaccine in a mouse melanoma model.

• Animals
• Cancer Vaccines/therapeutic use
• Disease Models, Animal
• Interleukin-27/therapeutic use
• Melanoma/prevention & control
• Melanoma/therapy
• Mice

• Natural Sciences and Engineering Research Council of Canada

• ablation
• cryoablation
• immuno-oncology
• intratumoral immunotherapy
• irreversible electroporation
• microwave ablation
• oncolytic virus
• radiofrequency ablation

• HMGB1
• Immunogenic cell death (ICD)
• antitumor vaccination
• apoptosis-inducing proteins
• calreticulin
• chemotherapy
• cold plasma jet
• oncolytic viruses

• Anti-tumor immunity
• Colorectal cancer
• Immunogenic cell death
• Photodynamic therapy
• TSPO

Immunotherapy represents the future of clinical cancer treatment. The type of cancer cell death determines the antitumor immune response and thereby contributes to the efficacy of anticancer therapy and long-term survival of patients. Induction of immunogenic apoptosis or necroptosis in cancer cells does activate antitumor immunity, but resistance to these cell death modalities is common. Therefore, it is of great importance to find other ways to kill tumor cells. Recently, ferroptosis has been identified as a novel, iron-dependent form of regulated cell death but whether ferroptotic cancer cells are immunogenic is unknown.

Ferroptotic cell death in murine fibrosarcoma MCA205 or glioma GL261 cells was induced by RAS-selective lethal 3 and ferroptosis was analyzed by flow cytometry, atomic force and confocal microscopy. ATP and high-mobility group box 1 (HMGB1) release were detected by luminescence and ELISA assays, respectively. Immunogenicity in vitro was analyzed by coculturing of ferroptotic cancer cells with bone-marrow derived dendritic cells (BMDCs) and rate of phagocytosis and activation/maturation of BMDCs (CD11c⁺CD86⁺, CD11c⁺CD40⁺, CD11c⁺MHCII⁺, IL-6, RNAseq analysis). The tumor prophylactic vaccination model in immune-competent and immune compromised (Rag-2^−/−) mice was used to analyze ferroptosis immunogenicity.

Ferroptosis can be induced in cancer cells by inhibition of glutathione peroxidase 4, as evidenced by confocal and atomic force microscopy and inhibitors’ analysis. We demonstrate for the first time that ferroptosis is immunogenic in vitro and in vivo. Early, but not late, ferroptotic cells promote the phenotypic maturation of BMDCs and elicit a vaccination-like effect in immune-competent mice but not in Rag-2^−/− mice, suggesting that the mechanism of immunogenicity is very tightly regulated by the adaptive immune system and is time dependent. Also, ATP and HMGB1, the best-characterized damage-associated molecular patterns involved in immunogenic cell death, have proven to be passively released along the timeline of ferroptosis and act as immunogenic signal associated with the immunogenicity of early ferroptotic cancer cells.

These results pave the way for the development of new therapeutic strategies for cancers based on induction of ferroptosis, and thus broadens the current concept of immunogenic cell death and opens the door for the development of new strategies in cancer immunotherapy.

• alarmins
• cytotoxicity
• immunogenicity
• immunologic
• immunotherapy
• phagocytosis
• vaccine

Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. Unlike other types of cancer, HCC can be treated with locoregional treatments (LRTs) such as radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). However, recurrences following LRTs are common, and strategies to improve long-term outcomes need to be developed. The exhaustion of anti-tumor immunity in HCC has been well established in many reports and the immunomodulatory effects of LRTs (enhancement of tumor antigen-specific T cell responses after RFA, reduction of effector regulatory T cells after TACE) have also been reported in several previous studies. However, a comprehensive review of previous studies and the possible roles of immunotherapy following LRTs in HCC are not known. In this review, we discuss the immunological evidence of current clinical trials using LRTs and combined immunotherapies, and the possible role of this strategy.

• HCC
• adjuvant treatment
• immunotherapy
• locoregional treatment

• cryoablation
• immune response
• immunotherapy
• melanoma
• tumors

• Animals
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/metabolism
• Cell Line, Tumor
• Cryosurgery
• Cytokines/metabolism
• Female
• Freezing
• Kinetics
• Lymphocytes, Tumor-Infiltrating/immunology
• Lymphocytes, Tumor-Infiltrating/metabolism
• Melanoma, Experimental/immunology
• Melanoma, Experimental/metabolism
• Melanoma, Experimental/pathology
• Melanoma, Experimental/surgery
• Mice, Inbred C57BL
• Myeloid Cells/immunology
• Myeloid Cells/metabolism
• Necrosis
• Skin Neoplasms/immunology
• Skin Neoplasms/metabolism
• Skin Neoplasms/pathology
• Skin Neoplasms/surgery
• Tumor Burden
• Mice

• hepatocellular carcinoma
• immune checkpoint inhibitors
• immunotherapy
• locoregional treatment

• cancer models
• antigen-presenting cells
• immune cell death

Active immunotherapy against cancer is based on immune system stimulation, triggering efficient and long-lasting antigen-specific immune responses. Immunization strategies using whole dead cells from tumor tissue, containing specific antigens inside, have become a promising approach, providing efficient lymphocyte activation through dendritic cells (DCs). In this work, we generate whole dead tumor cells from CT26, E.G7, and EL4 live tumor cells as antigen sources, which termed immunogenic cell bodies (ICBs), generated by a simple and cost-efficient starvation-protocol, in order to determine whether are capable of inducing a transversal anticancer response regardless of the tumor type, in a similar way to what we describe previously with B16 melanoma. We evaluated the anticancer effects of immunization with doses of ICBs in syngeneic murine tumor models. Our results showed that mice's immunization with ICBs-E.G7 and ICBs-CT26 generate 18% and 25% of tumor-free animals, respectively. On the other hand, all carrying tumor-animals and immunized with ICBs, including ICBs-EL4, showed a significant delay in their growth compared to not immunized animals. These effects relate to DCs maturation, cytokine production, increase in CD4+T-bet+ and CD4+ROR-γt+ population, and decrease of T regulatory lymphocytes in the spleen. Altogether, our data suggest that whole dead tumor cell-based cancer immunotherapy generated by a simple starvation protocol is a promising way to develop complementary, innovative, and affordable antitumor therapies in a broad spectrum of tumors.

A vaccine that induces potent, broad and sustained cell-mediated immunity, resulting in effective memory has the potential to restrict hepatitis C (HCV) virus infection. Early, multi-functional CD4⁺ and CD8⁺ T cell responses against non-structural protein 3 (NS3) have been associated with HCV clearance. Necrotic cells generate strong immune responses and represent a major antigenic source used by dendritic cells (DC) for processing and presentation, but there is conflicting evidence as to their immunogenicity in vaccination. Immunization with DC loaded with viral antigens has been done in the past, but to date the immunogenicity of live vs. necrotic DC vaccines has not been investigated. We developed a DC2.4 cell line stably expressing HCV NS3, and compared the NS3-specific responses of live vs. necrotic NS3 DC. Vaccination of mice with necrotic NS3 DC increased the breadth of T-cell responses and enhanced the production of IL-2, TNF-α, and IFN-γ by effector memory CD4⁺ and CD8⁺T cells, compared to mice vaccinated with live NS3 DC. A single dose of necrotic NS3 DC vaccine induced a greater influx and activation of cross-presenting CD11c⁺ CD8α⁺ DC and necrosis-sensing Clec9A⁺ DC in the draining lymph nodes. Furthermore, using a hydrodynamic challenge model necrotic NS3 DC vaccination resulted in enhanced clearance of NS3-positive hepatocytes from the livers of vaccinated mice. Taken together, the data demonstrate that necrotic DC represent a novel and exciting vaccination strategy capable of inducing broad and multifunctional T cell memory.

• HCV
• cell mediated immunity
• cross presentation
• hepatitis (C) virus
• necrosis
• vaccine

• TLR
• adjuvant
• immunogenic tumor cell vaccine
• irradiation

• Cancer immunotherapy
• Colorectal cancer
• Oncology
• Therapeutics

Apoptotic cells and cell fragments, especially those produced as a result of immunogenic cell death (ICD), are known to be a potential source of cancer vaccine immunogen. However, due to variation between tumours and between individuals, methods to generate such preparations may require extensive ex vivo personalisation. To address this, we have utilised the concept of in situ vaccination whereby an ICD inducing drug is injected locally to generate immunogenic apoptotic fragments/cells. These fragments are then adjuvanted by a co-administered cell reactive CpG adjuvant. We first evaluate means of labelling tumour cells with CpG adjuvant, we then go on to demonstrate in vitro that labelling is preserved following apoptosis and, furthermore, that the apoptotic body-adjuvant complexes are readily transferred to macrophages. In in vivo studies we observe synergistic tumour growth delays and elevated levels of CD4+ and CD8+ cells in tumours receiving adjuvant drug combination. CD4+/CD8+ cells are likewise elevated in the tumour draining lymph node and activated to a greater extent than individual treatments. This study represents the first steps toward the evaluation of rationally formulated drug-adjuvant combinations for in situ chemo-immunotherapy.

• Apoptosis
• Apoptotic body
• Cholesterol conjugate
• CpG
• Dendritic cell
• Doxorubicin
• Intratumoral

• dendritic cells
• glioma
• neurooncology

Neem leaf glycoprotein (NLGP), a natural immunomodulator, attenuates murine carcinoma and melanoma metastasis, independent of primary tumor growth and alterations in basic cellular properties (cell proliferation, cytokine secretion, etc.). Colonization event of invasion–metastasis cascade was primarily inhibited by NLGP, with no effect on metastasis-related invasion, migration, and extravasation. High infiltration of interferon γ (IFN-γ)–secreting cytotoxic CD8⁺ T cells [CD44⁺, CD69⁺, GranB⁺, IFN-γ⁺, and interleukin 2⁺] was documented in the metastatic site of NLGP-treated mice. Systemic CD8⁺ T cell depletion abolished NLGP-mediated metastasis inhibition and reappeared upon adoptive transfer of NLGP-activated CD8⁺ T cells. Interferon γ-secreting from CD8⁺ T cells inhibit the expression of angiogenesis regulatory vascular endothelial growth factor and transforming growth factor β and have an impact on the prevention of colonization. Neem leaf glycoprotein modulates dendritic cells (DCs) for proper antigen presentation by its DC surface binding and upregulation of MHC-I/II, CD86, and CCR7. Neem leaf glycoprotein–treated DCs specifically imprint CXCR3 and CCR4 homing receptors on activated CD8⁺ T cells, which helps to infiltrate into metastatic sites to restrain colonization. Such NLGP's effect on DCs is translation dependent and transcription independent. Studies using ovalbumin, OVA_257−264, and crude B16F10 antigen indicate MHC-I upregulation depends on the quantity of proteasome degradable peptide and only stimulates CD8⁺ T cells in the presence of antigen. Overall data suggest NLGP inhibits metastasis, in conjunction with tumor growth restriction, and thus might appear as a promising next-generation cancer immunotherapeutic.

• B16F10
• CD8+ T cells
• LLC
• NLGP
• antigen presentation
• dendritic cells
• metastasis
• metastatic colonization

• caspase 3 inhibitor
• immunogenic cell death
• radiotherapy

Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of caspase-3/7 was increased fourteen-fold as compared with four-fold in EL-4 cells. Moreover, while nsPEF treatments induced the release of the ICD hallmark HMGB1 in both cell lines, extracellular ATP was detected only in CT-26. Finally, in vaccination assays, CT-26 cells treated with nsPEF or doxorubicin equally impaired the growth of tumors at challenge sites eliciting a protective anticancer immune response in 78% and 80% of the animals, respectively. As compared to CT-26, both nsPEF- and mitoxantrone-treated EL-4 cells had a less pronounced effect and protected 50% and 20% of the animals, respectively. These results support our conclusion that nsPEF induce ER stress, accompanied by bona fide ICD.

• ablation
• apoptosis
• electroporation
• immunotherapy
• vaccine

• Cell death
• Locoregional therapy
• Radiofrequency ablation
• T cell
• Tumour immunology

• Animals
• CTLA-4 Antigen/antagonists & inhibitors
• Chemoembolization, Therapeutic
• Disease Models, Animal
• Humans
• Immunotherapy/methods
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Myeloid-Derived Suppressor Cells/physiology
• Radiofrequency Ablation

• Z99 CA999999 Intramural NIH HHS
• ZIA CL040015-10 Intramural NIH HHS
• ZID BC011242-10 Intramural NIH HHS

Accumulating data indicates that some cancer treatments can restore anticancer immunosurveillance through the induction of tumor immunogenic cell death (ICD). Nanosecond pulsed electric fields (nsPEF) have been shown to efficiently ablate melanoma tumors. In this study we investigated the mechanisms and immunogenicity of nsPEF-induced cell death in B16F10 melanoma tumors. Our data show that in vitro nsPEF (20–200, 200-ns pulses, 7 kV/cm, 2 Hz) caused a rapid dose-dependent cell death which was not accompanied by caspase activation or PARP cleavage. The lack of nsPEF-induced apoptosis was confirmed in vivo in B16F10 tumors. NsPEF also failed to trigger ICD-linked responses such as necroptosis and autophagy. Our results point at necrosis as the primary mechanism of cell death induced by nsPEF in B16F10 cells. We finally compared the antitumor immunity in animals treated with nsPEF (750, 200-ns, 25 kV/cm, 2 Hz) with animals were tumors were surgically removed. Compared to the naïve group where all animals developed tumors, nsPEF and surgery protected 33% (6/18) and 28.6% (4/14) of the animals, respectively. Our data suggest that, under our experimental conditions, the local ablation by nsPEF restored but did not boost the natural antitumor immunity which stays dormant in the tumor-bearing host.

• DAMPs
• RIPK3
• MLKL
• immunogenicity
• inflammation
• phosphatidylserine

The global tuberculosis epidemic is the most common cause of death after infectious disease worldwide. Increasing numbers of infections with multi- and extensively drug-resistant variants of the Mycobacterium tuberculosis complex, resistant even to newly discovered and last resort antibiotics, highlight the urgent need for an efficient vaccine. The protective efficacy to pulmonary tuberculosis in adults of the only currently available vaccine, M. bovis BCG, is unsatisfactory and geographically diverse. More importantly, recent clinical studies on new vaccine candidates did not prove to be better than BCG, yet. Here, we propose and discuss novel strategies to improve efficacy of existing anti-tuberculosis vaccines. Modulation of innate immune responses upon vaccination already provided promising results in animal models of tuberculosis. For instance, neutrophils have been shown to influence vaccine efficacy, both, positively and negatively, and stimulate specific antibody secretion. Modulating immune regulatory properties after vaccination such as induction of different types of innate immune cell death, myeloid-derived suppressor or regulatory T cells, production of anti-inflammatory cytokines such as IL-10 may have beneficial effects on protection efficacy. Incorporation of lipid antigens presented via CD1 molecules to T cells have been discussed as a way to enhance vaccine efficacy. Finally, concepts of dendritic cell-based immunotherapies or training the innate immune memory may be exploitable for future vaccination strategies against tuberculosis. In this review, we put a spotlight on host immune networks as potential targets to boost protection by old and new tuberculosis vaccines.

• CD1
• IL-10
• Mycobacterium tuberculosis
• cell death
• host-directed therapy
• neutrophils
• tuberculosis
• vaccine

• Cancer immunotherapy
• Cellular vaccine
• DNA vaccine
• Heat shock protein

Antigen cross-presentation is a crucial step in the assembly of an antitumor immune response leading to activation of naïve CD8 T cells. This process has been extensively used in clinical trials, in which dendritic cells generated in vitro are loaded with tumor antigens and then autotransplanted to the patients. Recently, the use of autologous transplant of dendritic cells fused with dying tumor cells has demonstrated good results in clinical studies. In this work, we generated a similar process in vivo by treating mice with dead tumor cells [cell bodies (CBs)] expressing the fusogenic protein of the infectious salmon anemia virus (ISAV). ISAV fusion protein retains its fusogenic capability when is expressed on mammalian cells in vitro and the CBs expressing it facilitates DCs maturation, antigen transfer by antigen-presenting cells, and increase cross-presentation by DCs in vitro. Additionally, we observed in the melanoma model that CBs with or without ISAV fusion protein reduce tumor growth in prophylactic treatment; however, only ISAV expressing CBs showed an increase CD4 and CD8 cells in spleen. Overall, our results suggest that CBs could be used as a complement with other type of strategies to amplify antitumor immune response.

• antitumor immune response
• b16 melanoma
• cell fusion
• cross-priming
• infectious salmon anemia virus

• Tien-Hsien liquid
• anticancer immunity
• cytotoxic T lymphocyte
• herbal mixture
• interferon-γ
• interleukin-2
• natural killer cell
• tumor necrosis factor α
• tumor suppression

• Animals
• Antineoplastic Agents/pharmacology
• Cell Line, Tumor
• Colonic Neoplasms/drug therapy
• Colonic Neoplasms/immunology
• Colonic Neoplasms/metabolism
• Drugs, Chinese Herbal/pharmacology
• Female
• Immunity/drug effects
• Interferon-gamma/metabolism
• Interleukin-2/metabolism
• Killer Cells, Natural/drug effects
• Killer Cells, Natural/immunology
• Killer Cells, Natural/metabolism
• Mice
• Mice, Inbred BALB C
• T-Lymphocytes, Cytotoxic/drug effects
• T-Lymphocytes, Cytotoxic/immunology
• T-Lymphocytes, Cytotoxic/metabolism
• Tumor Necrosis Factor-alpha/metabolism

• Ching-Hsing Medical Foundation, Taipei, Taiwan.

• Cytotoxic T-lymphocyte
• Immunity
• Radiation
• T-lymphocyte priming
• Tumor microenvironment

• Animals
• Antigens/immunology
• Apoptosis/radiation effects
• Disease Models, Animal
• Dose-Response Relationship, Radiation
• Mice
• Mouth Neoplasms/immunology
• Mouth Neoplasms/pathology
• Mouth Neoplasms/radiotherapy
• Ovalbumin/immunology
• Radiation, Ionizing
• T-Lymphocytes, Cytotoxic/immunology
• T-Lymphocytes, Cytotoxic/radiation effects
• Tumor Microenvironment

• ZIA DC000087 Intramural NIH HHS
• ZIA DC000087-01 Intramural NIH HHS

• Caspase-independent cell death
• Cisplatin
• Combined therapy
• Methylene blue
• Photodynamic therapy
• Photogem

• Animals
• Apoptosis/drug effects
• Cell Aggregation/drug effects
• Cell Communication/drug effects
• Cellular Microenvironment/drug effects
• Computer Simulation
• Drug Resistance, Neoplasm
• Humans
• Models, Biological
• Neoplasms/drug therapy
• Neoplasms/pathology
• Neoplasms/physiopathology
• Population Dynamics
• Tumor Burden/drug effects

• R01 CA170595 NCI NIH HHS
• U54 CA143970 NCI NIH HHS
• U54 CA193489 NCI NIH HHS

Photodynamic therapy (PDT) is a cancer treatment with a long-standing history. It employs the application of nontoxic components, namely a light-sensitive photosensitizer and visible light, to generate reactive oxygen species (ROS). These ROS lead to tumor cell destruction, which is accompanied by the induction of an acute inflammatory response. This inflammatory process sends a danger signal to the innate immune system, which results in activation of specific cell types and release of additional inflammatory mediators. Activation of the innate immune response is necessary for subsequent induction of the adaptive arm of the immune system. This includes the priming of tumor-specific cytotoxic T lymphocytes (CTL) that have the capability to directly recognize and kill cells which display an altered self. The past decades have brought increasing appreciation for the importance of the generation of an adaptive immune response for long-term tumor control and induction of immune memory to combat recurrent disease. This has led to considerable effort to elucidate the immune effects PDT treatment elicits. In this review we deal with the progress which has been made during the past 20 years in uncovering the role of PDT in the induction of the tumor-specific immune response, with special emphasis on adaptive immunity.

• antitumor immunity, regulatory T cells
• dendritic cells
• memory
• photodynamic tumor therapy
• tumor-specific immunity

Radiofrequency ablation (RFA) and cryoablation are alternative forms of therapy used widely in various pathological states, including treatment of carcinogenesis. The reason is that ablation techniques have ability of modulating the immune system. Furthermore, recent studies have applied this form of therapy on tumor microenvironment and in the systematic circulation. Moreover, RFA and cryoablation result in an inflammatory immune response along with tissue disruption. Evidence has demonstrated that these procedures affect carcinogenesis by causing a significant local inflammatory response leading to an immunogenic gene signature. The present review enlightens the current view of these techniques in cancer.

• ablation
• cancer
• cryoablation
• radiofrequency ablation
• tumor

• atmospheric pressure plasma
• cancer
• dielectric barrier discharge
• nanosecond pulsed electric field
• reactive species

• R01 EB013011 NIBIB NIH HHS

• Animals
• Apoptosis/immunology
• CD8-Positive T-Lymphocytes/immunology
• Caspase 8/metabolism
• Cell Survival
• Cross-Priming
• Dendritic Cells/immunology
• Mice
• Mice, Inbred C57BL
• NF-kappa B/metabolism
• NIH 3T3 Cells
• Receptor-Interacting Protein Serine-Threonine Kinases/genetics
• Receptor-Interacting Protein Serine-Threonine Kinases/metabolism
• Signal Transduction

• 5R01AI108685-02 NIAID NIH HHS
• R01 AI108685 NIAID NIH HHS
• T32 AI106677 NIAID NIH HHS
• 15689 Cancer Research UK
• R21CA185681 NCI NIH HHS
• R01 CA169291 NCI NIH HHS
• AI44848 NIAID NIH HHS
• R01AI108685 NIAID NIH HHS
• R21 CA185681 NCI NIH HHS
• R01 AI044828 NIAID NIH HHS