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Role of Nanoparticles in Cancer Immunotherapy
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Though tumor immunosurveillance hypothesis emphasizes the ability of immune cells to recognize and eliminate cancer cells; however, many patients develop cancer even in the presence of an apparently normal immune system. This indicates that tumor cells are able to escape immune surveillance. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Cancer immune evasion is a major limitation for developing an effective therapeutic approach to treat cancer. To have a successful anticancer immune response, the tumor-immunity cycle should be circulated uninterrupted [24]. Blockade at any step in the pathway leads to unresponsiveness. Cancer cells develop different strategies to interrupt the tumor-immunity cycle. In below sections, we review different escape mechanisms employed by cancer cells.
Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Cancers develop from early premalignant to advanced premalignant lesions, which then progress to become malignant cancers. Immunosurveillance of cancer can have three outcomes: “elimination” in which all cancer cells are completely removed by the immune system, “equilibrium” in which there is a “stalemate” between the immune system and the cancer, or “escape” in which there is unopposed progression of the cancer (Figure 9.3). Having no preexisting immunity allows for unopposed progression of cancer (escape). Some patients will have some antitumor antibodies and relevantly targeted T cells (i.e., preexisting immunity), which may result in either equilibrium or escape depending on the strength of the immunity. However, if this preexisting immunity is boosted using a prophylactic cancer vaccine, the result may be equilibrium or even elimination of the tumor cells, with potentially lifelong protection through immune memory elicited by the vaccine.
Radiation Immunology
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Natural killer (NK) cells are naturally occurring cells that destroy a variety of tumor cells and cultured cell lines. Therefore, they are considered to play an important role in immunosurveillance mechanisms against spontaneously occurring tumor cells in vivo. It has been reported that 1000 rads stimulates the cytotoxic activity of NK cells, whereas a higher dose (3000 rads) completely destroys the NK activity of these cells.11,12 It has been suggested that the radiation sensitivity of NK cells is controlled by X-linked codominant genes. MRL mice spontaneously develop massive nonneoplastic T cell proliferation and autoimmune disease, which kills 50% of the mice by 5–6 months of age. However, the total lymphoid irradiation (3400 rads) given at the age of3 months (time of clinical onset of disease) produced 100% survival at the age of 9 months, whereas the whole-body irradiation (300 rads) produced 82% survival.13 By 9 months of age, 92% of the nonirradiated mice died. It was found13 that after 6 months of postirradiation, the irradiated animals had normal supressor T cell function (Con A induced); the helper T cell activity was lower than the nonirradiated control.13
Nanoparticles releasing immunogenic cell death inducers upon near-infrared light exposure
Published in OncoImmunology, 2022
Oliver Kepp, Giulia Cerrato, Allan Sauvat, Guido Kroemer
The success of cancer immunotherapy strongly depends on the (re)invigoration of cancer immunosurveillance. Therapeutically relevant anticancer immune responses can be stimulated by a restricted panel of chemotherapeutics, targeted agents, oncolytics as well as by radiotherapy, all of which are activators of defined immunogenic cell stress and cell death (ICD) circuitries.1 The spatially defined sequential emission of danger associated molecular patterns (DAMPs) in the course of ICD defines the level of adjuvanticity of succumbing malignant cells and the consequent initiation of T cell-mediated adaptive immunity. DAMPs emitted in the course of ICD trigger the attraction, activation and maturation and thus the functional engagement of antigen presenting dendritic cells (DCs). The attraction and homing of DCs is driven by the liberation of adenosine triphosphate (ATP) and annexin A1 (ANXA1) by malignant cells, respectively. Moreover, relocation and subsequent exposure of calreticulin (CALR) serves as a phagocytic signal for DCs. CALR exposure, together with the production of type I interferons and the exodus of high mobility group box 1 (HMGB1), triggers tumor antigen transfer and DC maturation. In sum, ICD elicits the tumor antigen-specific DC-mediated priming of cytotoxic T lymphocytes (CTL), resulting in anticancer immunity, tumor lysis and disease control that finally outlasts treatment discontinuation.2
Immune dysfunction in inborn errors of immunity causing malignancies
Published in Expert Review of Clinical Immunology, 2021
In recent years, numerous new genetic reasons for human inborn errors of immunity (IEI) have been identified [1,2]. Knowing the monogenic causes helps us predict future encountering illness, especially malignancies that determine prognosis. Regarding immune defense during diseases, the model of surveillance was first used by Burnet in 1963 [3], later extended by immunoediting encompassing immunosurveillance that describes the active role of the immune system in maintaining self-protection by destroying invaders and pre-malignant cells [4,5]. Defective immunosurveillance poses individuals to increased risk of malignancy. Following infections, malignancy is the second leading cause of death among immunodeficient patients [4,6]. The type of malignancy and the mechanisms underlying this predisposition is varied among different categories of IEI [7]. The combination of diagnostic delay/challenge, increased comorbidity, infections and toxicity usually results in a poorer outcome and survival compared to immunocompetent patients [8–10]. Herein, we discuss the concept of malignancy in IEI by dissecting the diseases based on their molecular defects.
Crizotinib and ceritinib trigger immunogenic cell death via on-target effects
Published in OncoImmunology, 2021
Adriana Petrazzuolo, Maria Perez-Lanzon, Peng Liu, M. Chiara Maiuri, Guido Kroemer
Cancer does not develop without the failure of immunosurveillance.1 Accordingly, the clinical efficacy of cancer therapies heavily relies on the (re)establishment of anticancer immune responses. Immunogenic cell death (ICD) is an immunologically “noisy” modality of cell death accompanied by the exposure or release of danger-associated molecular patterns (DAMPs) that alert innate immune effectors (mostly dendritic cells) to finally launch a cognate immune response (mostly mediated by cytotoxic T lymphocytes) against dead-cell antigens.2,3 Prominent ICD-linked DAMPs include adenosine triphosphate (ATP, which is released during cell death), calreticulin (CALR, which is exposed on the cell surface at a premortem stage), high mobility group box 1 (HMGB1, which exits the nucleus and is released from cells as they succumb) and type-I interferons (which are actively synthesized and activate other downstream genes including genes coding for chemokines to favor an immune response).2 ICD was initially discovered in the context of cytotoxic anticancer chemotherapies.4 However, it is important to note that only a fraction of cytotoxicants is able to induce ICD, correlating with their clinical long-term efficacy against cancer as well as with their capacity to inhibit DNA-to-RNA transcription.5