Cancer Immunoprevention: A New Approach to Intercept Cancer Early

Umar, Asad

doi:10.1158/1940-6207.capr-14-0213

Cited by 23 publications

(19 citation statements)

References 23 publications

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“…From a preventive point of view, this leads to the concept of cancer immunoprevention, i.e. the opportunity to further decrease tumor risk through the stimulation of immune defenses [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Cancer immunoprevention: from mice to early clinical trials

et al. 2018

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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.

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Section: Introductionmentioning

confidence: 99%

Cancer immunoprevention: from mice to early clinical trials

et al. 2018

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“…Preclinical and clinical evidences have revealed that early transformed cells express antigens that allow the immune system to recognize them and initiate an immune response (15, 16). To overcome the antineoplastic effects of the immune system, tumor cells may transmit immune suppressive signals to the tumor microenvironment that enable cancer progression (17, 18).…”

Section: Introductionmentioning

confidence: 99%

PD-1 Blockade Prevents the Development and Progression of Carcinogen-Induced Oral Premalignant Lesions

Wang

Xie

Wang

et al. 2017

Cancer Prevention Research

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Oral squamous cell carcinoma (OSCC) is preceded by progressive oral premalignant lesions (OPLs). Therefore, therapeutic strategies that prevent malignant progression of OPLs are expected to reduce the incidence of OSCC development. Immune checkpoint inhibitors that target the interaction of programmed death receptor 1 (PD-1) on T cells with the PD-1 ligand PD-L1 on cancer cells have been shown to extend the survival of patients with advanced OSCC. Here, we used the 4-Nitroquinoline-1-oxide (4-NQO) mouse model of oral carcinogenesis to test the hypothesis that PD-1 blockade may control the progression of OPLs. Mice were exposed to 4-NQO in their drinking water and then randomly assigned to two treatment groups that received either a blocking antibody for PD-1 or a control IgG. We found that anti-PD-1 treatment significantly reduced the number of oral lesions that developed in these mice, and prevented malignant progression. Low-grade dysplastic lesions responded to PD-1 blockade with a significant increase in the recruitment of CD8+ and CD4+ T cells and the accumulation of CTLA-4+ T cells in their microenvironment. Notably, PD-1 inhibition was accompanied by induction of interferon-γ, STAT1 activation and the production of the T cell effector granzyme B in infiltrating cells, and by the induction of apoptosis in the epithelial cells of the oral lesions, suggesting that T cell activation mediates the immunopreventive effects of anti-PD-1. These results support the potential clinical benefit of PD-1 immune checkpoint blockade to prevent OSCC development and progression and suggest that CTLA-4 inhibitors may enhance the preventive effects of anti-PD-1.

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“…Natural antibodies are important for innate immune defense against potential pathogens and in the recognition and removal of abnormal cells (Grönwall et al, 2012[ 10 ]). It is the latter function that likely explains the significance of natural antibodies in tumor surveillance and cancer prevention (Umar, 2014[ 33 ]). Natural antibodies typically bind to the carbohydrate moieties and glycans expressed by precancerous and cancerous cells (Vollmers and Brandlein, 2009[ 36 ]), although natural antibodies also bind to a variety of “neoepitopes” that become exposed when autologous cells are disrupted (Ailus and Palosuo, 1995[ 3 ]; Casali and Schettino, 1996[ 5 ]; Guilbert et al, 1982[ 11 ]; Lacroix-Desmazes et al, 1998[ 12 ]; Logtenberg, 1990[ 15 ]; Lydyard et al, 1990[ 16 ]; Parker et al, 1997[ 21 ]; Quan et al, 1997[ 23 ]; Spalter et al, 1999[ 29 ]; Stahl et al, 2000[ 30 ]; Vassilev and Veleva, 1996[ 34 ]).…”

Section: Introductionmentioning

confidence: 99%