@article{fdf3c13e7bdd440397ff336827b5082d,
title = "Immunotherapeutic Transport Oncophysics: Space, Time, and Immune Activation in Cancer",
abstract = "Immuno-oncology has gained momentum thanks to the success of strategies aimed at enhancing immune-mediated antitumor response. The field of immunotherapeutic transport oncophysics investigates the physical processes that drive cancer immunotherapies. This review discusses three main aspects that determine the outcome of an immunotherapy-based treatment from a physical point of view; (i) space, the distribution of cancer and immune cells within tumor masses, (ii) time, the temporal dynamic of immune response against tumors, and (iii) activity, the ability of immune cell populations to suppress cancer. Upon introducing these topics with examples from the literature, we investigate in detail two cases where the interplay between space, time, and activation variables determines immune response: nanodendritic cell vaccines and immunosuppression in ovarian cancer.",
keywords = "cancer, immuno-oncology, immunotherapy, physics of cancer, transport oncophysics",
author = "Sara Nizzero and Haifa Shen and Mauro Ferrari and Bruna Corradetti",
note = "Funding Information: B.C. acknowledges support through the S?r Cymru II scheme, funded by European Union's Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 663830 and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF). The authors also acknowledge support from National Institutes of Health (NIH) grant U54CA210181. The authors further acknowledge Matthew G. Landry for support in designing and producing the graphical elements in the manuscript. Funding Information: B.C. acknowledges support through the S{\^e}r Cymru II scheme, funded by European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No 663830 and the Welsh European Funding Office (WEFO) under the European Regional Development Fund (ERDF). The authors also acknowledge support from National Institutes of Health (NIH) grant U54CA210181 . The authors further acknowledge Matthew G. Landry for support in designing and producing the graphical elements in the manuscript. Abscopal effect a distant therapeutic effect originated from a systemic response to localized treatment. Adaptive immune system comprises highly specialized cells and processes aimed at controlling and eliminating pathogens through the recognition of exogenous antigens. An adaptive immune response (e.g., T cell response) creates a memory of specific pathogen recognition, which represents the principle of vaccination strategies. Adoptive T cell therapy cytotoxic T cells from cancer patients are selected, expanded and re-administered to the same patient to amplify the effect of the adaptive immune response to the tumor. Cancer immunotherapy therapeutic approach aimed at stimulating the immune system to provide cancer prevention and treatment. Chimeric antigen receptor T (CAR-T) cell therapy a type of adoptive T cell therapy, where T cells are manipulated to express tumor-specific receptors thus enhancing their antitumor activity. Cold tumors malignancies characterized by reduced presence or activity of effector immune infiltrates. Exosomes nanoscopic biological particles naturally released by cells and characterized by a precise targeting potential that allows for the activation or repression of specific molecular cascades in targeted cells. Activity and function of exosomes can be tailored by modifying their composition and cargo through parental cells conditioning or with the addition of functional drugs. Hot tumors malignancies characterized by enhanced effector immune infiltration and activation. Immune checkpoint inhibitors cells of the immune systems are able to recognize foreign particulates or harmful cells through the activation of specific molecules, called checkpoints, initiating immune response. PD-1, Tim-3, and CTLA-4 are examples of checkpoint molecules and are expressed by immune cells such as T cells. Upon engaging their ligands, checkpoint molecules elicit inhibitory signals in the immune cells expressing them. Checkpoint-inhibitor immunotherapies (i.e., anti-PD-L1, anti-PD-1, and anti-CTLA-4 antibodies) block the binding of checkpoint molecules to their ligands. Immunogenic cell death (ICD) a form of apoptosis characterized by the release of DC-stimulating antigens, resulting in the activation of a T cell-mediated antitumor immune response. ICD can be initiated through several therapeutic agents including cytotoxic agents, RT, and photodynamic therapy. Immunotherapeutic transport oncophysics (ImmTRO) approach aiming at understanding the role of transport in regulating immune response to tumors. Innate immune system the body{\textquoteright}s first response to pathogens. The innate immune system recruits immune cells to tissues through the release of cytokines (inflammation), removes damaged cells or pathogens, and activates the adaptive immune system through antigen presentation. It comprises cells such as macrophages, DCs, neutrophils, and natural killer cells . Transport oncophysics (TRO) approach that aims at understanding cancer, cancer treatments, and drug delivery from the transport standpoint [ 3 ]. Transport phenotype functional classification of the tumor microenvironment based on active or passive transport properties of the tumor microenvironment. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jan,
doi = "10.1016/j.trecan.2019.11.008",
language = "English (US)",
volume = "6",
pages = "40--48",
journal = "Trends in Cancer",
issn = "2405-8033",
publisher = "Cell Press",
number = "1",
}