Tumor Immunity and Immunotherapy for HPV-Related Cancers.
Ontology highlight
ABSTRACT:
SUBMITTER: Shamseddine AA
PROVIDER: S-EPMC8338882 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cancer-related diseases represent the second overall cause of death worldwide. Human papilloma virus (HPV) is an infectious agent which is mainly sexually transmitted and may lead to HPV-associated cancers in both men and women. Almost all cervical cancers are HPV-associated, however, an increasing number of head and neck cancers (HNCs), especially oropharyngeal cancer, can be linked to HPV infection. Moreover, anogenital cancers, including vaginal, vulvar, penial, and anal cancers, represent a subset of HPV-related cancers. Whereas testing and prevention of cervical cancer have significantly improved over past decades, anogenital cancers remain more difficult to confirm. Current clinical trials including patients with HPV-related cancers focus on finding proper testing for all HPV-associated cancers as well as improve the currently applied treatments. The HPV viral oncoproteins, E6 and E7, lead to degradation of, respectively, p53 and pRb resulting in entering the S phase without G1 arrest. These high-risk HPV viral oncogenes alter numerous cellular processes, including DNA repair, angiogenesis, and/or apoptosis, which eventually result in carcinogenesis. Additionally, a comprehensive analysis of gene expression and alteration among a panel of DNA double strand breaks (DSB) repair genes in HPV-negative and HPV-positive HNC cancers reveals differences pointing to HPV-dependent modifications of DNA repair processes in these cancers. In this review, we discuss the current knowledge regarding HPV-related cancers, current screening, and treatment options as well as DNA damage response-related biological aspects of the HPV infection and clinical trials.
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Project description:Epigenetic mechanisms, including DNA methylation, histone post-translational modifications, and chromatin structure regulation, are critical for the interactions between tumor and immune cells. Emerging evidence shows that tumors commonly hijack various epigenetic mechanisms to escape immune restriction. As a result, the pharmaceutical modulation of epigenetic regulators, including 'writers', 'readers', 'erasers', and 'remodelers', is able to normalize the impaired immunosurveillance and/or trigger antitumor immune responses. Thus, epigenetic targeting agents are attractive immunomodulatory drugs and will have major impacts on immuno-oncology. Here, we discuss epigenetic regulators of the cancer-immunity cycle and current advances in developing epigenetic therapies to boost anticancer immune responses, either alone or in combination with current immunotherapies.
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Project description:Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.
| S-EPMC6300347 | biostudies-literature
Project description:Background:
The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. Researchers want to test this on human papilloma virus (HPV)-associated cancers.
Objective:
- The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (Anti-HPV E6) can shrink tumors associated with HPV and test the toxicity of this treatment.
Eligibility:
- Adults age 18-66 with an HPV-16-associated cancer.
Design:
* Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed
* Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti HPV E6 cells. {Leukapheresis is a common procedure, which removes only the white blood cells from the patient.}
* Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the anti HPV E6 cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment.
Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits take up to 2 days.
| 2177506 | ecrin-mdr-crc
Project description:Persistent infection with carcinogenic human papillomaviruses (HPV) causes the majority of anogenital cancers and a subset of head and neck cancers. The HPV genome is frequently found integrated into the host genome of invasive cancers. The mechanisms of how it may promote disease progression are not well understood. Thoroughly characterizing integration events can provide insights into HPV carcinogenesis. Individual studies have reported limited number of integration sites in cell lines and human samples. We performed a systematic review of published integration sites in HPV-related cancers and conducted a pooled analysis to formally test for integration hotspots and genomic features enriched in integration events using data from the Encyclopedia of DNA Elements (ENCODE). Over 1,500 integration sites were reported in the literature, of which 90.8% (N?=?1,407) were in human tissues. We found 10 cytobands enriched for integration events, three previously reported ones (3q28, 8q24.21 and 13q22.1) and seven additional ones (2q22.3, 3p14.2, 8q24.22, 14q24.1, 17p11.1, 17q23.1 and 17q23.2). Cervical infections with HPV18 were more likely to have breakpoints in 8q24.21 (p?=?7.68 × 10(-4) ) than those with HPV16. Overall, integration sites were more likely to be in gene regions than expected by chance (p?=?6.93 × 10(-9) ). They were also significantly closer to CpG regions, fragile sites, transcriptionally active regions and enhancers. Few integration events occurred within 50 Kb of known cervical cancer driver genes. This suggests that HPV integrates in accessible regions of the genome, preferentially genes and enhancers, which may affect the expression of target genes.
| S-EPMC6749823 | biostudies-literature
Project description:The immune system is composed of immune as well as non-immune cells. As this system is a well-established component of human papillomavirus- (HPV)-related carcinogenesis, high risk human papillomavirus (hrHPV) prevents its routes and mechanisms in order to cause the persistence of infection. Among these mechanisms are those originated from stromal cells, which include the cancer-associated fibroblasts (CAFs), the myeloid-derived suppressor cells (MDSCs) and the host infected cells themselves, i.e. the keratinocytes. These types of cells play central role since they modulate immune cells activities to create a prosperous milieu for cancer development, and the knowledge how such interactions occur are essential for prognostic assessment and development of preventive and therapeutic approaches. Nevertheless, the precise mechanisms are not completely understood, and this lack of knowledge precluded the development of entirely efficient immunotherapeutic strategies for HPV-associated tumors. As a result, an intense work for attaining how host immune response works, and developing of effective therapies has been applied in the last decade. Based on this, this review aims to discuss the major mechanisms of immune and non-immune cells modulated by hrHPV and the potential and existing immunotherapies involving such mechanisms in HPV-related cancers. It is noticed that the combination of immunotherapies has been demonstrated to be essential for obtaining better results, especially because the possibility of increasing the modulating capacity of the HPV-tumor microenvironment has been shown to be central in strengthening the host immune system.
| S-EPMC6034319 | biostudies-literature
Project description:Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.
| S-EPMC4964648 | biostudies-literature
Project description:Background: Our objective was to characterize cancer immunity marker expression in gynecologic cancers and compare immune landscapes between gynecologic tumor subtypes and with non-gynecologic solid tumors. Methods: RNA expression levels of 51 cancer-immunity markers were analyzed in patients with gynecologic cancers vs. non-gynecologic cancers, and normalized to a reference population of 735 control cancers, ranked from 0-100, and categorized as low (0-24), moderate (25-74), or high (75-100) percentile rank. Results: Of the 72 patients studied, 43 (60%) had ovarian, 24 (33%) uterine, and 5 (7%) cervical cancer. No two immune profiles were identical according to expression rank (0-100) or rank level (low, moderate, or high). Patients with cervical cancer had significantly higher expression level ranks of immune activating, pro-inflammatory, tumor infiltrating lymphocyte markers and checkpoints than patients with uterine or ovarian cancer (p<0.001 for all comparisons). However, there were no significant differences in immune marker expression between uterine and ovarian cancers. Tumors with PD-L1 TPS =>1% versus 0% had significantly higher expression levels of pro-inflammatory markers (58 vs. 49%, p=0.0004). Compared to patients with non-gynecologic cancers, more patients with gynecologic cancers express high levels of IDO-1 (44 vs. 13%, p<0.001), LAG3 (35 vs. 21%, p=0.008) and IL10 (31 vs. 15%, p=0.002.) Conclusions: Patients with gynecologic cancers have complex and heterogeneous immune landscapes that are distinct from patient to patient and from other solid tumors. High levels of IDO1 and LAG3 suggest that clinical trials with IDO1 inhibitors or LAG3 inhibitors, respectively, may be warranted in gynecologic cancers.
| S-EPMC9949233 | biostudies-literature
Project description:Transplant recipients have elevated cancer risk including risk of human papillomavirus (HPV)-associated cancers of the cervix, anus, penis, vagina, vulva and oropharynx. We examined the incidence of HPV-related cancers in 187 649 US recipients in the Transplant Cancer Match Study. Standardized incidence ratios (SIRs) compared incidence rates to the general population, and incidence rate ratios (IRRs) compared rates across transplant subgroups. We observed elevated incidence of HPV-related cancers (SIRs: in situ 3.3-20.3, invasive 2.2-7.3), except for invasive cervical cancer (SIR 1.0). Incidence increased with time since transplant for vulvar, anal and penile cancers (IRRs 2.1-4.6 for 5+ vs. <2 years). Immunophenotype, characterized by decreased incidence with HLA DRB1:13 and increased incidence with B:44, contributed to susceptibility at several sites. Use of specific immunosuppressive medications was variably associated with incidence; for example, tacrolimus, was associated with reduced incidence for some anogenital cancers (IRRs 0.4-0.7) but increased incidence of oropharyngeal cancer (IRR 2.1). Thus, specific features associated with recipient characteristics, transplanted organs and medications are associated with incidence of HPV-related cancers after transplant. The absence of increased incidence of invasive cervical cancer highlights the success of cervical screening in this population and suggests a need for screening for other HPV-related cancers.
| S-EPMC4049182 | biostudies-literature