Spotlight

Abstract

Zeng et al., pp.268–273 The human immune system can recognize and react to tumor-associated antigens (TAA). Identifying TAA based on their recognition by antibodies provides molecular details of the immune response and suggests that detection, diagnosis and prognosis of cancer by serological markers may yet be possible. Most antigens react with only a few, if any, allogeneic sera, making it difficult and expensive to investigate antibody responses against a large panel of TAA that covers a wide spectrum of patients with a particular cancer. The authors propose that purifying individual proteins might not be necessary if dominant B-cell epitopes could be identified. Using the antigen NY-ESO-1 as a prototype, they tested a synthetic peptide of the epitope ESO:1–40 and found that the peptide was as sensitive as the recombinant protein for detecting antibodies against the tumor antigen. Previous studies indicate that such antibodies appear mainly in patients with advanced disease, and this particular antigen is expressed in a variety of human cancers, including lung, breast, ovarian, prostate, melanoma and others. The authors suggest that the epitope-based approach could dramatically simplify antibody detection in cancer patients. de Jong et al., pp.274–282 Human papillomavirus (HPV) type 16 is the high risk type found most frequently in cervical cancer; HPV oncoproteins E6 and E7 are constitutively expressed in tumor cells and are required to maintain malignant phenotype, making them attractive targets for immunotherapy. Tumor-related immunosuppression often accompanies advanced cervical cancer, leading researchers to suspect that adoptive transfer of tumor-specific T cells might have a better chance of working than a therapeutic vaccine. Previous work in mice has shown that adoptive T cell therapy can eradicate solid tumors. The technique has also been applied to patients with metastatic melanoma, with mixed success. The authors investigated the feasibility of enriching for T cells that recognize the E6 antigen from the peripheral blood of healthy donors on the basis of interferon-gamma secretion. The obtained T cell populations successfully recognized distinct epitopes within the E6 antigen. There are several advantages to this approach. Enrichment of antigen-specific T cells secreting IFN-gamma ensures selection of T cells with an optimal cytokine profile for anti-tumor immunity, and enriching for antigen-specific T cells helps minimize alloreactivity and risk of graft-vs.-host disease. These results represent a strong first step toward developing a T cell-based therapy for advanced cervical cancer by showing that HPV16E6-specific T cells, which may be useful for eradicating tumor cells, can be collected from the peripheral blood cells of healthy donors. Increased purity of HPV16E6-specific CD4+ T-cells by extended culture period before isolation of antigen-specific cells Hanaoka et al., pp.317–322 The role of tobacco smoking in breast cancer has been of great interest to the public health community, particularly since tobacco smoke contains known carcinogens, and most established risk factors for breast cancer cannot be modified. However, the relationship between smoking and breast cancer has been foggy at best; some studies have shown a link, while others found no relationship and still others have suggested a protective effect from smoking. Previous analyses have demonstrated that tobacco-related carcinogens do reach human breast tissue. However, the antiestrogenic effects of tobacco smoke could decrease breast cancer risk, particularly among postmenopausal women. The authors studied a large cohort of middle-aged Japanese women and attempted to determine the risk of breast cancer as it relates to smoking status: e.g., active smokers, nonsmokers who have not been exposed to tobacco smoke regularly, and nonsmokers who are regularly exposed to smoke in their homes or workplaces (“passive smokers”). Active smoking increased breast cancer risk among premenopausal women; premenopausal, passive smokers showed a smaller increase in risk. No increase in risk associated with smoking was found for postmenopausal women. This is the first prospective study to link active smoking with breast cancer risk in Asian women.