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Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy. Cancers 2023, 15, 5385. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cancers15225385  \nAcademic Editor: Eishi Ashihara  \nReceived: 16 October 2023  \nRevised: 7 November 2023  \nAccepted: 10 November 2023  \nPublished: 13 November 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Division of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [zchen3@uams.edu](zchen3@uams.edu) (Z.C.); [srsingh@uams.edu](srsingh@uams.edu) (S.S.)  \n2 Department of Urology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [maydin@uams.edu](maydin@uams.edu) (A.M.A.); [tlangford@uams.edu](tlangford@uams.edu) (T.L.)  \n3 Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [smaraboyina@uams.edu](smaraboyina@uams.edu)  \n4 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; [gokdenneriman@uams.edu](gokdenneriman@uams.edu)  \n* Correspondence: [stu@uams.edu](stu@uams.edu)  \nSimple Summary: According to the stem cell theory of cancer, we should be judicious with immunotherapy in cancer care. When we do not realize that cancer originates from a stem cell and has stem-ness capabilities, immunotherapy could be gratifying for the wrong reasons and challenging with a cautionary tale.  \nAbstract: A simple way to understand the immune system is to separate the self from non-self. If it is self, the immune system tolerates and spares. If it is non-self, the immune system attacks and destroys. Consequently, if cancer has a stem cell origin and is a stem cell disease, we have a serious problem and a major dilemma with immunotherapy. Because many refractory cancers are more self than non-self, immunotherapy may become an uphill battle and pyrrhic victory in cancer care. In this article, we elucidate cancer immunity. We demonstrate for whom, with what, as well as when and how to apply immunotherapy in cancer care. We illustrate that a stem cell theory of cancer affects our perspectives and narratives of cancer. Without a pertinent theory about cancer's origin and nature, we may unwittingly perform misdirected cancer research and prescribe misguided cancer treatments. In the ongoing saga of immunotherapy, we are at a critical juncture. Because of the allure and promises of immunotherapy, we will be treating more patients not immediately threatened by their cancer. They may have more to lose than to gain, if we have a misconception and if we are on a wrong mission with immunotherapy. According to the stem cell theory of cancer, we should be careful with immunotherapy. When we do not know or realize that cancer originates from a stem cell and has stem-ness capabilities, we may cause more harm than good in some patients and fail to separate the truth from the myth about immunotherapy in cancer care.  \nKeywords: cancer vaccine; immunotherapy; cancer stem cell; hyper-progression; heterogeneity; microenvironment; autoimmunity; microbiome  \n1. Introduction  \nIt is difficult to separate, at times, the myth from the truth.  \n—Bob Kane  \nWhen we know the origin of something, we will know many important things about that something. Knowing th","cbCaiqQvzZsHBaBv","https://ap.wps.com/l/cbCaiqQvzZsHBaBv","pdf",656832,17,"English","# Introduction\n## Myth versus truth about cancer origin\n# Stem cell theory of cancer\n## Unifying understanding of origin, hallmarks, and microenvironment\n# Immunotherapy: promises and limitations","[{\"question\":\"What does the article propose about applying immunotherapy in cancer care?\",\"answer\":\"It states that a stem cell theory shapes when and how immunotherapy should be applied. The article aims to clarify for whom, with what approaches, and under what timing to use immunotherapy appropriately.\"}]","Stem Cell Origin of Cancer - Clinical Implications for Cancer Immunity and Immunotherapy | PDF",1790215713,43]