The flip side of immune surveillance: immune dependency

Prehn, Richmond T.; Prehn, Liisa M.

doi:10.1111/j.1600-065x.2008.00609.x

Cited by 28 publications

(32 citation statements)

References 101 publications

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“…15,16 As shown in Table 3, at each stage of carcinogenesis the immune system can either inhibit or facilitate the process. A further complicating factor is the observation that tumor growth itself can cause immunosuppression.…”

Section: Review Of the Role Of The Immune System In Neoplasiamentioning

confidence: 99%

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Bugelski¹,

Volk²,

Walker³

et al. 2010

Int J Toxicol

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Many immunosuppressive drugs are associated with an increased risk of B-cell lymphoma, squamous cell carcinoma, and Kaposi sarcoma. Thirteen immunosuppressive drugs have been tested in 2-year carcinogenicity studies (abatacept; azathioprine; busulfan; cyclophosphamide; cyclosporine; dexamethasone; everolimus; leflunomide; methotrexate; mycophenolate mofetil; prednisone; sirolimus; and tacrolimus) and in additional models including neonatal and genetically modified mice; chemical, viral, ultraviolet, and ionizing radiation co-carcinogenesis, and in models with transplanted tumor cells. The purpose of this review is to outline the mechanisms by which immunosuppressive drugs can influence neoplasia, to summarize the available preclinical data on the 13 drugs, and to critically review the performance of the models. A combination of primary tumor and metastasis assays conducted with transplanted cells may provide the highest value for hazard identification and can be applied on a case-by-case basis. However, for both small molecules and therapeutic proteins, determining the relative risk to patients from preclinical data remains problematic. Classifying immunosuppressive drugs based on their mechanism of action and hazard identification from preclinical studies and a prospective pharmacovigilance program to monitor carcinogenic risk may be a feasible way to manage patient safety during the clinical development program and postmarketing.

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Section: Review Of the Role Of The Immune System In Neoplasiamentioning

confidence: 99%

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Bugelski¹,

Volk²,

Walker³

et al. 2010

Int J Toxicol

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“…This is congruent with reports of anti-tumor antibodies to a variety of antigens in ovarian cancer (30, 37, 38). It has been hypothesized that autoimmunity increases the risk for cancer (32, 35, 39, 40) and that a weak tumor-directed immune response can stimulate tumor growth (41, 42). …”

Section: Introductionmentioning

confidence: 99%

Autoantibodies to Mesothelin in Infertility

Luborsky

Edassery

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background According to extensive epidemiological data, infertility is associated with increased ovarian cancer risk. Previous studies showed that both women with infertility and those with ovarian cancer have autoantibodies to ovarian antigens. The objective was to determine if women with infertility have antibodies to mesothelin, a well characterized ovarian cancer antigen. Methods Sera were obtained from women with infertility (n=109), ovarian cancer (n=28), benign ovarian tumors or cysts (n=24) and from healthy women (n=152). Infertility included those with a risk for ovarian cancer; endometriosis (n=23), ovulatory dysfunction (n=17), premature ovarian failure (n=25) and unexplained infertility (n=44). Sera were assayed for mesothelin antibodies and for circulating mesothelin antigen by immunoassay and compared to assay control sera (n=16) to determine a positive result. Results Mesothelin antibodies were significantly more frequent in women with prematurely reduced ovarian function including ovulatory dysfunction (59%), ovarian failure (POF) (44%) and unexplained infertility (25%) compared to controls. In contrast, women with endometriosis, who also have a high risk for ovarian cancer, did not have mesothelin antibodies. Serum levels of mesothelin were rarely elevated in women with infertility but were high in most patients with ovarian cancer. Conclusions and Significance We show for the first time that antibodies to mesothelin, a well characterized ovarian cancer antigen, occur in some women with epidemiologic risk for ovarian cancer. The results suggest it may be possible to identify which women with infertility have ovarian cancer risk.

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“…An interesting and perhaps philosophical take on this comes from Drs. Prehn who suggested tumor and host evolve along a bell-shaped immune response curve reaching a perfect equilibrium at the top when immunity is most conducive to tumor growth and that basically any attempt at shifting this balance, be it through IT, RT, or otherwise, would inevitably alter the perfect “tumor-immune dance” and slow tumor growth (175, 176). …”

Section: Resultsmentioning

confidence: 99%

A Century of Radiation Therapy and Adaptive Immunity

Schaue

2017

Front. Immunol.

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The coming of age for immunotherapy (IT) as a genuine treatment option for cancer patients through the development of new and effective agents, in particular immune checkpoint inhibitors, has led to a huge renaissance of an old idea, namely to harness the power of the immune system to that of radiation therapy (RT). It is not an overstatement to say that the combination of RT with IT has provided a new conceptual platform that has re-energized the field of radiation oncology as a whole. One only has to look at the immense rise in sessions at professional conferences and in grant applications dealing with this topic to see its emergence as a force, while the number of published reviews on the topic is staggering. At the time of writing, over 97 clinical trials have been registered using checkpoint inhibitors with RT to treat almost 7,000 patients, driven in part by strong competition between pharmaceutical products eager to find their market niche. Yet, for the most part, this enthusiasm is based on relatively limited recent data, and on the clinical success of immune checkpoint inhibitors as single agents. A few preclinical studies on RT–IT combinations have added real value to our understanding of these complex interactions, but many assumptions remain. It seems therefore appropriate to go back in time and pull together what actually has been a long history of investigations into radiation and the immune system (Figure 1) in an effort to provide context for this interesting combination of cancer therapies.

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The flip side of immune surveillance: immune dependency

Cited by 28 publications

References 101 publications

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

Autoantibodies to Mesothelin in Infertility

A Century of Radiation Therapy and Adaptive Immunity

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