Dataset Information

Tumor Immunity and Immunotherapy for HPV-Related Cancers.

ABSTRACT: Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific treatments, and discuss future directions. Although responses across these studies have been modest to date, a deeper understanding of HPV-related tumor biology and immunology may prove instrumental for the development of more efficacious immunotherapeutic approaches. SIGNIFICANCE: HPV modulates the microenvironment to create a protumorigenic state of immune suppression and evasion. Our understanding of these mechanisms has led to the development of immunomodulatory treatments that have shown early clinical promise in patients with HPV-related malignancies. This review summarizes our current understanding of the interactions of HPV and its microenvironment and provides insight into the progress and challenges of developing immunotherapies for HPV-related malignancies.

SUBMITTER: Shamseddine AA

PROVIDER: S-EPMC8338882 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Tumor Immunity and Immunotherapy for HPV-Related Cancers.

Shamseddine Achraf A AA Burman Bharat B Lee Nancy Y NY Zamarin Dmitriy D Riaz Nadeem N

Cancer discovery 20210514 8

Human papillomavirus (HPV) infection drives tumorigenesis in the majority of cervical, oropharyngeal, anal, and vulvar cancers. Genetic and epidemiologic evidence has highlighted the role of immunosuppression in the oncogenesis of HPV-related malignancies. Here we review how HPV modulates the immune microenvironment and subsequent therapeutic implications. We describe the landscape of immunotherapies for these cancers with a focus on findings from early-phase studies exploring antigen-specific t ...[more]

PMID: 33990345

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Project description:It has been previously proposed that some types of cancer cells reprogram their metabolic pathways, favoring the metabolism of glucose by aerobic glycolysis (Warburg effect) instead of oxidative phosphorylation, mainly because the mitochondria of these cells are damaged, thus displaying mitochondrial dysfunction. However, in several cancers, the mitochondria do not exhibit any dysfunction and are also necessary for the tumor's growth and maintenance. Remarkably, if the mitochondria are dysfunctional, specific processes associated with the release of cytochrome c (cyt c), such as apoptosis, are significantly impaired. In these cases, cellular biotherapies such as mitochondrial transplantation could restore the intrinsic apoptotic processes necessary for the elimination of cancers. On the other hand, if the mitochondria are in good shape, drugs that target the mitochondria are a valid option for treating the related cancers. Famously, the mitochondria are targeted by the human papillomavirus (HPV), and HPV-related cancers depend on the host's mitochondria for their development and progression. On the other hand, the mitochondria are also important during treatment, such as chemotherapy, since they are key organelles for the increase in reactive oxygen species (ROS), which significantly increases cell death due to the presence of oxidative stress (OS). In this way, the mitochondria in HPV infection and in the development of HPV-related cancer could be targeted to reduce or eliminate HPV infections or HPV-related cancers. To our knowledge, there was no previous review specifically focusing on this topic, so this work aimed to summarize for the first time the potential use of mitochondria-targeting drugs, providing molecular insights on the main therapeutics developed so far in HPV infection and HPV-related cancer. Thus, we reviewed the mechanisms associated with HPV-related cancers, with their early proteins and mitochondrial apoptosis specifically induced by different compounds or drugs, in which these molecules induce the production of ROS, the activation of proapoptotic proteins, the deactivation of antiapoptotic proteins, the loss of mitochondrial membrane potential (Δψm), cyt c release, and the activation of caspases, which are all events which lead to the activation of mitochondrial apoptosis pathways. This makes these compounds and drugs potential anticancer therapeutics that target the mitochondria and could be exploited in future biomedical strategies.

Dataset Information

Tumor Immunity and Immunotherapy for HPV-Related Cancers.

Publications

Tumor Immunity and Immunotherapy for HPV-Related Cancers.

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