Abstract
Background: Relatively little is known about the role of the humoral immune system in melanoma. Tumor infiltrating B cells in melanoma patients have been associated with increased T cell activation in tumors as well as improved patient survival. Immunoglobulins may play an important part in the anti-tumor immune response. We hypothesized that increased levels of pre-diagnostic serum Ig may be protective against melanoma development. Hence, we evaluated associations between pre-diagnostic serum markers of the immunoglobulin A (IgA), IgG and IgM, and risk of developing melanoma in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study.Methods: Study participants aged ≥20 years with baseline measurements of IgG, IgA and IgM taken between 1985 and 1996 were selected (n = 29,876). All individuals were free from melanoma at baseline and 162 study participants developed melanoma during follow up. Cox proportional hazards regression was carried out for medical cut-offs of IgA, IgG, and IgM.Results: Compared to the reference level of 6.10–14.99 g/l, we observed a positive but not significant association with risk of melanoma for those with IgG levels <6.10 g/L [HR: 1.05 (95% CI 0.39–2.86)] and an inverse association for those with IgG levels ≥15.00 g/L [HR: 0.60 (95% CI 0.34–1.05); Ptrend = 0.08]. No associations with serum IgA or IgM were identified.Conclusions: The humoral response might provide a protective role against the development of melanoma, mediated through IgG. Further research is needed to characterize this response which may be exploitable for development of future therapies.
Highlights
Since the 1970s, the incidence of cutaneous melanoma has been rapidly increasing [1]
A growing body of evidence has revealed the immunogenicity of melanoma; the majority of research has been directed at the role of T cells in melanoma, and there is relatively little data on the humoral immune system and melanoma
Certain studies have revealed immunomodulatory mechanisms that support a Th2-biased immune response associated with reduced mature B cell responses and production of immunoglobulin isotypes, such as IgG4, in tumor microenvironments and the circulation of patients with melanoma [7,8,9,10]
Summary
Since the 1970s, the incidence of cutaneous melanoma has been rapidly increasing [1]. Certain studies have revealed immunomodulatory mechanisms that support a Th2-biased immune response associated with reduced mature B cell responses and production of immunoglobulin isotypes, such as IgG4, in tumor microenvironments and the circulation of patients with melanoma [7,8,9,10]. These re-educated humoral responses are thought to participate in cancer-associated inflammation and may moderate the potency of otherwise cytotoxic antibodies, to prevent immune-driven elimination of melanoma and may even negatively affect prognosis [7, 9, 11, 12]. We evaluated associations between pre-diagnostic serum markers of the immunoglobulin A (IgA), IgG and IgM, and risk of developing melanoma in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study
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