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Biologically Targeted Agents in Head and Neck Cancers
Published in John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford, Head & Neck Surgery Plastic Surgery, 2018
Kevin J. Harrington, Magnus T. Dillon
There is evidence from both the laboratory and the clinic that radiation therapy can cause immunogenic cell death.106–108 Furthermore, there are both pre-clinical and clinical data to demonstrate that immune checkpoint inhibition may enhance this effect and lead to systemic activity of a local therapy (e.g. radiation).109, 110 These observations, combined with the excitement over single-agent activity of immune checkpoint inhibition, have led to a number of clinical studies that are combining immune checkpoint inhibitors with ionizing radiation. At present, there are no substantial reports of this approach in the literature, but it is likely that studies evaluating palliative hypofractionated radiotherapy and radical standard fractionation (with and without platin-based chemotherapy) will be reported in the coming years. This strategy certainly seems to hold promise, especially as a means of using intensive locoregional therapy as a means of generating systemic activity (and protection) against metastatic disease recurrence.
Radiobiology and Hadron Therapy
Published in Manjit Dosanjh, Jacques Bernier, Advances in Particle Therapy, 2018
Eleanor A. Blakely, Manjit Dosanjh
The demonstrated ability of radiation therapy to drive immunogenic modulation and promote immune-mediated killing of tumour cells in a variety of human carcinomas of distinct origin and genotype gives it broad clinical applicability for cancer therapy. There is a surge of interest in immunotherapy for cancer which offers an opportunity for the field of radiation oncology because mounting evidence suggests that radiation-induced cell death simultaneously contributes to an immunologically active process known as immunogenic cell death wherein apoptotic and necrotic dying tumour cells release a variety of tumour-associated antigens (TAAs) that can potentially be exploited to stimulate robust tumour-specific immune responses for effective disease control. Ionising radiation (RT) causes changes in the tumour microenvironment that can lead to intratumoural as well as distal immune modulation – the so-called abscopal phenomenon.
Immunotherapy of peritoneal carcinomatosis
Published in Wim P. Ceelen, Edward A. Levine, Intraperitoneal Cancer Therapy, 2015
Michael A. Ströhlein, Markus M. Heiss
Catumaxomab enhanced T-cell activation [CD69, CD107A (LAMP1), HLA-DR, and PD-1(PDCD1) expression] and stimulated inflammatory CD4(+) TH1 and CD8(+) TH1 to release IFN-γ but failed to trigger TH17 cells. Engagement of CD16-expressing cells caused upregulation of TRAIL (TNFSF10) and costimulatory CD40 and CD80 molecules. CatmAb promoted tumor cell death associated with ATP release and strongly synergized with oxaliplatin for the exposure of the three hallmarks of immunogenic cell death (calreticulin, HMGB1, and ATP) [38].
A HER2-targeted antibody-novel DNA topoisomerase I inhibitor conjugate induces durable adaptive antitumor immunity by activating dendritic cells
Published in mAbs, 2023
Xiaoding Tan, Peng Fang, Kaiying Li, Meng You, Yuxia Cao, Hui Xu, Xiaohong Zhu, Lu Wang, Xin Wei, Haiying Wen, Wendi Li, Lei Shi, Xiaowei Sun, Dongan Yu, Huikai Zhu, Zhenzhen Wang, Datao Liu, Hui Shen, Wei Zhou, Maomao An
Most antitumor therapies, especially radiotherapy and chemotherapy, are considered to be directly tumoricidal, killing tumor cells or inducing cell cycle arrest. Because chemotherapy targets not only tumor cells but also rapidly proliferating host immune cells, investigators have assumed that cytotoxic chemotherapeutics induce immunosuppressive rather than immunostimulatory effects. As a result, the importance of host immune responses to cytotoxic drugs has been neglected.21–25 Similarly, the importance of an intact host immune system has not been sufficiently considered in developing ADC products. For example, ADC preclinical in vivo efficacy studies are usually conducted on immunodeficient mice, such as athymic nude mice to investigate the direct killing effect of the ADC on human tumor cells or patient-derived tumors. In such experiments, the importance of the immune system, especially T cells and B cells, has been ignored because their functions or numbers are impaired in the models. Several research groups challenged this conventional notion, and have found that dying tumor cells, whether induced by ADCs or chemotherapeutics, can be immunogenic, a phenomenon termed immunogenic cell death. The DAMPs released by tumor cells committed to ICD can be acquired by APCs, especially dendritic cells and macrophages, and finally active cytotoxicity T cells, connecting innate and adaptive immunity.
A nanoparticle-based tour de force for enhancing immunogenic cell death elicited by photodynamic therapy
Published in OncoImmunology, 2022
The therapeutic outcome of oncological regimen depends on the onset of anticancer immune responses as they can be stimulated by radiotherapy, certain targeted drugs, a selected panel of chemotherapeutics, as well as local oncolytic agents, all of which are potent activators of immunogenic cell stress and cell death routines.1 Immunogenic cell death (ICD) is associated with the emission of a defined set of danger associated molecular patterns (DAMPs) by malignant cells that in their correct spatial and temporal appearance trigger the functional engagement of dendritic cells (DCs) and the consequent onset of T cell-mediated adaptive immunity. DAMPs emitted in the course of ICD include adenosine triphosphate (ATP) and annexin A1 (ANXA1), which serve as chemoattractant and homing signal for DCs, respectively. Calreticulin that translocates from the endoplasmic reticulum lumen (ER) on to the cytoplasmic membrane guides DC-mediated phagocytosis, and the exodus of high mobility group box 1 (HMGB1) triggers final antigen presenting cell (APC) maturation. Altogether ICD stimulates DC-mediated tumor antigen cross presentation to cytotoxic T lymphocytes (CTL), resulting in anticancer immunogenicity manifesting with interferon γ (IFN γ)-mediated tumor lysis and the generation of memory T cells facilitating disease control beyond treatment discontinuation.2
Avelumab: search for combinations of immune checkpoint inhibition with chemotherapy
Published in Expert Opinion on Biological Therapy, 2021
Tumor cells release neoantigens which are presented by MHC Class II proteins with the help of costimulatory CD80/CD86 dendritic cells (A) to CD3-positive T cells which can express CTLA-4 (D) and PD-1 (E) for the regulation of the activity of the immune system. The cytotoxic T cells recognize tumor cells via neoantigens and MHC Class I receptors (B). Downregulation of the immune system can be reversed by ICIs against CTLA-4, PD-1, or PD-L1 on tumor cells (C). Cytotoxic drugs such as cisplatin, Pemetrexed, docetaxel, vincristine, and others induce (partial) cell death and the release of neoantigens in association with upregulation of PD-L1 on viable cells left as well as a reduction of Tregs and MDSCs. Furthermore, the agents may be involved in stimulating leucocyte infiltration into the tumor area (F). In this way ‘immunogenic’ cell death helps to stimulate the immune system and to enhance the effects of ICIs.