Juan C. Osorio

Beyond T Cells: IgA Incites Immune Recognition in Endometrial Cancer

While T cells are established major players in antitumor immunity, tumor-associated B cells and antibodies have recently emerged as critical components in modulating immunity in the tumor microenvironment. In the current issue of Cancer Research, Mandal and colleagues show that tumor-infiltrating B cells are associated with improved outcomes in endometrial cancers. Mechanistically, the investigators demonstrate that the immune response is mediated by class-switched IgA binding to the polymeric immunoglobulin receptor in tumor cells, resulting in tumor cell–intrinsic activation of inflammatory pathways. These findings highlight that coordinated B-cell and T-cell responses may predict improved outcomes in patients with endometrial cancer and set the groundwork to further investigate the mechanisms by which humoral immunity could be exploited for cancer immunotherapy.See related article by Mandal et al., p. 859

Body mass index and adiposity influence responses to immune checkpoint inhibition in endometrial cancer

BACKGROUNDObesity is the foremost risk factor in the development of endometrial cancer (EC). However, the impact of obesity on the response to immune checkpoint inhibitors (ICI) in EC remains poorly understood. This retrospective study investigates the association among BMI, body fat distribution, and clinical and molecular characteristics of EC patients treated with ICI.METHODSWe analyzed progression-free survival (PFS) and overall survival (OS) in EC patients treated with ICI, categorized by BMI, fat-mass distribution, and molecular subtypes. Incidence of immune-related adverse events (irAEs) after ICI was also assessed based on BMI status.RESULTS524 EC patients were included in the study. Overweight and obese patients exhibited a significantly prolonged PFS and OS compared with normal BMI patients after treatment with ICI. Multivariable Cox's regression analysis confirmed the independent association of overweight and obesity with improved PFS and OS. Elevated visceral adipose tissue (VAT) was identified as a strong independent predictor for improved PFS to ICI. Associations between obesity and OS/PFS were particularly significant in the copy number-high/TP53abnormal (CN-H/TP53abn) EC molecular subtype. Finally, obese patients demonstrated a higher irAE rate compared with normal BMI individuals.CONCLUSIONObesity is associated with improved outcomes to ICI in EC patients and a higher rate of irAEs. This association is more pronounced in the CN-H/TP53abn EC molecular subtype.FUNDINGNIH/NCI Cancer Center; MSK Gerstner Physician Scholars Program; National Center for Advancing Translational Sciences (NCATS); Cycle for Survival; Breast Cancer Research Foundation.