Role of Nanoparticles in Cancer Immunotherapy
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
The concept of tumor immune surveillance, i.e., the ability of immune cells to detect and kill the nascent tumor cells, was first of all proposed independently by M.F. Burnet and L. Thomas in 1950s [9, 10]. The idea of cancer immunosurveillance laid the foundation of tumor immunology and cancer immunotherapy. In later years, many clinical and animal studies supported the hypothesis of tumor immunosurveillance. For example, immunodeficient animals show high rate of tumor incidence and this trend is seen in immunodeficient human patients as well. However, immunosurveillance hypothesis could not clarify why the tumor cells still grow despite the ability of immune cells to recognize and eliminate them. To explain this observation, a more inclusive and updated hypothesis was proposed by Dr. Robert Schrieber in 2002, which is popularly known as ‘cancer immunoediting’ [11, 12] (Figure 12.1). The cancer immunoediting hypothesis incorporates both the aspects of immune system, namely, immunoprotective and immunoselective role. The immune system not only protects the host, but can also shape the immunogenicity of tumor. Cancer immunoediting encompasses in three stages defined by the three “Es” namely ‘Elimination (equivalent to immune surveillance)’, ‘Equilibrium’, and ‘Escape’. Cancer cells evade the immune responses by employing or pirating the different immune suppression mechanism that were used to prevent overactivation of immune cells during immune homeostasis.
Tumor immunology
Gabriel Virella in Medical Immunology, 2019
It is now well understood that the immune system is not only able to survey and control neoplastic processes, but that by applying this immune pressure it also transforms the tumor and its microenvironment. Cancer immunoediting is the general process by which tumor cells “edit” themselves and/or their microenvironment in response to an antitumor immune response leading to cancer progression. Immune selection leads to the generation of tumor escape variants, and there are multiple mechanisms that lead to the immune evasion by tumors as outlined in Figure 26.2.
Cancer Immunology
John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie in Basic Sciences Endocrine Surgery Rhinology, 2018
The discovery and identification of tumour antigens has helped scientists begin to understand the key steps in an anti-tumour immune response. In animal models, the encounter between the immune system and tumours initiates a process termed ‘immunoediting’.70 This process can bring about three outcomes: elimination of the tumour; tumour equilibrium, in which there is immune selection of less immunogenic tumours during an anti-tumour immune response;71 and tumour escape, the growth of tumour variants that resist immune destruction.
Identification and editing of stem-like cells in methylcholanthrene-induced sarcomas
Published in OncoImmunology, 2019
Emilie T. E. Gross, Carlos D. Peinado, Yujin Jung, Semi Han, Beichen Liu, Endi K. Santosa, Jack D. Bui
Cancer immunoediting refers to the process by which tumor cells and immune cells interact with one another, leading to a sculpting of the cancer cell repertoire.25–27 Immunoediting begins on a substrate of highly immunogenic “unedited” cancer cells that can be completely eliminated by the immune system. In some instances a mixture of edited and unedited cancer cells are not completely eliminated and in fact can co-exist over long periods of time in the presence of immune pressure, representing an equilibrium phase.28,29 From this phase “edited” cancer cells can emerge, and these escaped cells can proceed to grow and become clinically significant. Edited cancer cells presumably have evaded immunity, but whether they have accumulated stem-like properties compared to unedited cells is not known.
Enhanced protection of C57 BL/6 vs Balb/c mice to melanoma liver metastasis is mediated by NK cells
Published in OncoImmunology, 2018
Friedrich Foerster, Sebastian Boegel, Rosario Heck, Geetha Pickert, Nina Rüssel, Sebastian Rosigkeit, Matthias Bros, Stephanie Strobl, Leonard Kaps, Misbah Aslam, Mustafa Diken, John Castle, Ugur Sahin, Andrea Tuettenberg, Ernesto Bockamp, Detlef Schuppan
The immune system usually protects against carcinogenesis by immunosurveillance.2 However, through a process known as immunoediting, malignant cells are first eliminated, then exist in equilibrium and finally escape the anti-tumor immune response.3 In melanoma, the immune escape is facilitated by a tolerogenic, immunosuppressive tumor microenvironment which is constituted of regulatory T-cells (Tregs), myeloid derived suppressor cells (MDSC) and tumor-associated macrophages (TAM).4,5 Cancer immunotherapy aims at preventing or reversing such immunoediting and melanoma is generally considered to be a susceptible cancer entity.6 Indeed, so called checkpoint inhibitors, which target PD1/PD-L1 or CTLA4, have recently achieved impressive responses in melanoma patients.7 However, the immunology of cancer is far from being fully understood and only a fraction of patients responds to the currently available therapies which makes studies on (metastatic) melanoma a necessity.
Neoantigen characteristics in the context of the complete predicted MHC class I self-immunopeptidome
Published in OncoImmunology, 2019
Scott D. Brown, Robert A. Holt
Immunoediting is a well accepted phenomenon that occurs during cancer development.31 By comparing observed mutations from immune-exposed TCGA tumors to in silico generated mutations, we were able to detect signals of immune-evasion within the TCGA data. It is important to note that our in silico mutations are random and do not necessarily confer the same cancer growth advantage, or in fact any biological relevance, that is likely found in the set of TCGA mutations and thus are used as a measure of baseline pMHC generation. Compared to in silico mutations, we observed a general trend of decreased immunogenicity for expressed TCGA mutations, and an increase for non-expressed mutations. This supports the view that the majority of TCGA tumors are immune-edited, as we see higher immunogenicity from non-expressed SNVs than would be expected by chance. This could be the result of immune-editing over time shaping the mutational profile of these cancer cells through accumulation of mutations that would be potentially immunogenic if expressed, but are immunologically inconsequential when present in non-expressed genes. Under this framework, we also identified samples that showed evidence of a suppressed immune response, permitting relatively more immunogenic mutations in expressed genes. These subjects demonstrate decreased progression free survival, supporting the concept that these individuals harbour tumours which have suppressed the natural immune response to the tumor.
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