Abstract
In developed countries, lung cancer is the leading cause of cancer-related death in both sexes. Although cigarette smoking represents the principal risk factor for lung cancer in females, the higher proportion of this neoplasm among non-smoking women as compared with non-smoking men implies distinctive biological aspects between the two sexes. Gender differences depend not only on genetic, environmental, and hormonal factors but also on the immune system, and all these aspects are closely interconnected. In the last few years, it has been confirmed that the immune system plays a fundamental role in cancer evolution and response to oncological treatments, specifically immunotherapy, with documented distinctions between men and women. Consequently, in order to correctly assess cancer responses and disease control, considering only age and reproductive status, the results of studies conducted in female patients would probably not categorically apply to male patients and vice versa. The aim of this article is to review recent data about gender disparities in both healthy subjects’ immune system and lung cancer patients; furthermore, studies concerning gender differences in response to lung cancer immunotherapy are examined.
Highlights
In the last few years, it has been confirmed that immune system plays a fundamental role in cancer evolution and response to oncological treatments, immunotherapy, with documented distinctions between men and women [5]
Sex differences in lymphocyte subsets are described in Asian, European, and African populations; women show a greater antibody response than men, with higher basal immunoglobulin levels and B-cell numbers. This last evidence could be due to a significant up-regulation in B cells in females as compared with males, as described in a global analysis of B-cell gene-expression signatures performed by Fan and Coll on a small group of both healthy subjects and patients with systemic lupus erythematosus disease [9,10,11,12]
The difference in efficacy between the two sexes treated with immune checkpoints inhibitors (ICIs) was significant (p = 0.0019) [31,32]. In both of the aforementioned meta-analyses, despite the large number of patients analyzed, a lower number of women was considered. This is a potential limitation to observe a significant interaction between sexes and ICIs efficacy as well as trials’ heterogeneity, different cancer types considered, and lacking data about hormonal and Programmed death-ligand 1 (PD-L1) status according to sex, as already described for the previous meta-analyses
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Sex differences in lymphocyte subsets are described in Asian, European, and African populations; women show a greater antibody response than men, with higher basal immunoglobulin levels and B-cell numbers This last evidence could be due to a significant up-regulation in B cells in females as compared with males, as described in a global analysis of B-cell gene-expression signatures performed by Fan and Coll on a small group of both healthy subjects and patients with systemic lupus erythematosus disease [9,10,11,12]. Further studies are needed to better clarify the impact of cigarette smoke on immune reactions and the impact on lung cancer risk in both sexes
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