Editors' ChoiceCancer

MYCing progress against immunosuppression-associated cancers

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Science Translational Medicine  28 Jan 2015:
Vol. 7, Issue 272, pp. 272ec16
DOI: 10.1126/scitranslmed.aaa5553

It has been known for years that immune suppression increases the risk of cancer. Chronically immunosuppressed populations, including individuals with HIV/AIDS and solid organ transplant recipients, face heightened risks of numerous malignancies. Although the association is strongest for infection-related cancers such as lymphoma, Kaposi’s sarcoma, hepatocellular carcinoma, and cervical cancer, there is also a clear association with several noninfection-associated cancers such as lung cancer, thyroid cancer, and kidney cancer.

For most of these cancers, immunosuppression also conveys a worse prognosis. Even after matching for stage and histologic subtype, these patients face lower response rates, shorter duration of disease control, and worse overall survival. These inferior outcomes reflect multiple factors. Reduced immune function not only contributes to tumor development, but also to locoregional progression and metastatic potential. Furthermore, concurrent immunosuppression substantially complicates and increases the toxicity of chemotherapy administration.

Moving beyond these clinical observations, Chao et al. have compared the molecular characteristics of diffuse large B-cell lymphoma (DLBCL) from patients with and without HIV infection. Pulling from more than 10 years of data from the Kaiser Permanente registry in California, they matched 80 HIV-infected DLBCL patients 1:1 with 80 HIV-uninfected DLBCL patients by age, gender, and race. They used immunohistochemistry to examine 23 markers in such categories as cell cycle regulators, B-cell activators, and antiapoptotic proteins. The researchers found that, compared with HIV-uninfected cases, HIV-related DLBCL was more likely to express cMYC (87% versus 56%), BCL6 (45% versus 10%), PKC-beta2 (61% versus 4%), MUM1 (59% versus 14%), and CD44 (87% versus 56%), whereas expression of p27 was reduced (39% versus 75%). cMYC expression was also independently associated with increased 2-year mortality in the HIV-infected cohort (RR 3.09).

This study provides molecular insights into the more aggressive clinical course of HIV-related DLBCL. In particular, increased cMYC may partly account for this trend and may even serve as a therapeutic target for this disease in the future.

C. Chao et al., A comparative study of molecular characteristics of diffuse large B-cell lymphoma from patients with and without human immunodeficiency virus infection. Clin. Cancer Res. 10.1158/1078-0432.CCR-14-2083 (2015). [Abstract]

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