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• W2099806568 abstract "We thank Whiteside and Ferrone for their insightful CCR Translations article (1) in response to our article (2). They accurately describe how our knowledge of the role of the immune system in tumor prognosis has evolved since the 1980s. Their explanation of the beneficial role of tumor-infiltrating plasma cells via antibody-dependent cellular cytotoxicity, similar to the tumor antigen–specific therapeutic antibodies rituximab, cetuximab, or trastuzumab (Fig. 1 in ref. 1), is quite elegant. Nevertheless, to avoid any misunderstanding of our work, 2 specific aspects should be addressed. The first is that the B-cell plasma cell metagene, but not the T-cell metagene, had a significant prognostic impact on metastasis-free survival (third paragraph in ref. 1). In fact, the B-cell plasma cell metagene (or IGKC as a single marker) was associated with metastasis-free interval (MFI) in univariate and multivariate analyses. However, the T-cell metagene is also associated with MFI in the univariate analysis in 3 independent clinical cohorts of fast proliferating carcinomas (Table 2 in ref. 3). Only when adjusted to the B-cell/plasma cell metagene does the T-cell metagene lose its significance. This is explained by the high degree of correlation between the B-cell/plasma and T-cell metagenes, which in turn corresponds to the observation that a tumor with many infiltrating plasma cells also contains a high number of T cells. However, there is also a subgroup of patients with low B-cell/plasma cell and high T cell metagene expression. Therefore, we should avoid the misunderstanding that T-cell infiltration is not relevant in breast cancer.The second comment refers to the Janus-faced nature of the humoral immune system. Clearly, plasma cell infiltration (indicated by the single biomarker IGKC) is associated with better prognosis in breast, lung, and colon cancer. However, a minority of the 60-gene B-cell/plasma cell metagene is associated not with better but with worse prognosis. Do these genes indicate that plasma cells can turn “evil” and also initiate protumor effects, possibly by secreting cytokines that stimulate tumor growth (4)? Although the discovery of tumor-infiltrating plasma cell dates back to the 1980s (5), the quest for a deeper understanding of the Janus-faced humoral immune system has just begun.See the Response, p. 305No potential conflicts of interest were disclosed." @default.
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• W2099806568 date "2013-01-01" @default.
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• W2099806568 title "IGKC and Prognosis in Breast Cancer–Letter" @default.
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• W2099806568 doi "https://doi.org/10.1158/1078-0432.ccr-12-2818" @default.
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