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Cancer immunoprevention: from mice to early clinical trials.

ABSTRACT: Cancer immunoprevention is based on the fact that a functioning immune system controls tumor onset and development in humans and animals, thus leading to the idea that the enhancement of immune responses in healthy individuals could effectively reduce cancer risk later in life. Successful primary immunoprevention of tumors caused by hepatitis B and papilloma viruses is already implemented at the population level with specific vaccines. The immunoprevention of human tumors unrelated to infectious agents is an outstanding challenge. Proof-of-principle preclinical studies in genetically-modified or in carcinogen-exposed mice clearly demonstrated that vaccines and other immunological treatments induce host immune responses that effectively control tumor onset and progression, eventually resulting in cancer prevention. While a straightforward translation to healthy humans is currently unfeasible, a number of pioneering clinical trials showed that cancer immunoprevention can be effectively implemented in human cohorts affected by specific cancer risks, such as preneoplastic/early neoplastic lesions. Future developments will see the implementation of cancer immunoprevention in a wider range of conditions at risk of tumor development, such as the exposure to known carcinogens and genetic predispositions.

SUBMITTER: Palladini A

PROVIDER: S-EPMC6003025 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Cancer immunoprevention: from mice to early clinical trials.

Palladini Arianna A Landuzzi Lorena L Lollini Pier-Luigi PL Nanni Patrizia P

BMC immunology 20180615 1

Cancer immunoprevention is based on the fact that a functioning immune system controls tumor onset and development in humans and animals, thus leading to the idea that the enhancement of immune responses in healthy individuals could effectively reduce cancer risk later in life. Successful primary immunoprevention of tumors caused by hepatitis B and papilloma viruses is already implemented at the population level with specific vaccines. The immunoprevention of human tumors unrelated to infectious ...[more]

PMID: 29902992

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Project description:Invasive cancers typically evade immune surveillance through profound local and systemic immunosuppression, preventing their elimination or control. Targeting immune interventions to prevent or intercept premalignant lesions, before significant immune dysregulation has occurred, may be a more successful strategy. The field of cancer immune interception and prevention is nascent, and the scientific community has been slow to embrace this potentially most rational approach to reducing the global burden of cancer. This may change due to recent promising advances in cancer immunoprevention including the use of vaccines for the prevention of viral cancers, the use of cancer-associated antigen vaccines in the setting of precancers, and the development of cancer-preventative vaccines for high-risk individuals who are healthy but carry cancer-associated heritable genetic mutations. Furthermore, there is increasing recognition of the importance of cancer prevention and interception by national cancer organizations. The National Cancer Institute (NCI) recently released the National Cancer Plan, which includes cancer prevention among the top priorities of the institute. The NCI's Division of Cancer Prevention has been introducing new funding opportunities for scientists with an interest in the field of cancer prevention: The Cancer Prevention-Interception Targeted Agent Discovery Program and The Cancer Immunoprevention Network. Moreover, the Human Tumor Atlas Network is spearheading the development of a precancer atlas to better understand the biology of pre-invasive changes, including the tissue microenvironment and the underlying genetics that drive carcinogenesis. These data will inform the development of novel immunoprevention/immuno-interception strategies. International cancer foundations have also started recognizing immunoprevention and immune interception with the American Association for Cancer Research, Cancer Research UK and the Society for Immunotherapy of Cancer each implementing programming focused on this area. This review will present recent advances, opportunities, and challenges in the emerging field of cancer immune prevention and immune interception.

Project description:TARGET (Tumour characterisation to Guide Experimental Targeted therapy) seeks to optimise the pathway for molecular characterisation of all patients entering early phase cancer trials to inform clinical decision-making on optimal therapy. Performance status (PS) was developed to assess a patient’s ability to perform a variety of activities to further inform clinical decision making on optimal therapy including appropriate inclusion in clinical trials. However, the quality of present algorithms to assess performance status are limited and based on a semi-quantitative clinician assessment. In particular, a common eligibility criterion for entry into early phase cancer clinical trials is a life expectancy of >3 or 6 months. Here we investigate proteomics as a means of more objective and quantitative assessment of both performance status and thus likely prognosis prior to clinical trial enrolment. Improved patient stratification at enrolment would reduce the number of patients unnecessarily exposed to potentially toxic drugs and decrease withdrawal from trials. Plasma samples from patients enrolled into the TARGET trial were analysed using the mass spectrometry (MS) technique: Sequential window acquisition of all theoretical fragment ion spectra (SWATH) MS. SWATH-MS was used on a discovery cohort of 73 patients to identify proteins that could differentiate patients into either a good or poor prognosis. A three-protein panel showed a stronger prediction of overall survival (p = 0.000086) compared to PS (p = 0.001). This panel was then tested against a validation cohort of 77 patients. The panel was determined as being a significant (p = 0.000451) predictor of overall survival whereas PS was not significant. The panel had a receiver operating characteristic curve area under the curve (AUC) of 0.73 in the validation set; the AUC of PS was 0.54. This signature can now be developed further in larger patient populations to assess its utility in a clinical setting.

Dataset Information

Cancer immunoprevention: from mice to early clinical trials.

Publications

Cancer immunoprevention: from mice to early clinical trials.

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