IL2 Targeted to CD8+ T Cells Promotes Robust Effector T-cell Responses and Potent Antitumor Immunity.

IL2 signals pleiotropically on diverse cell types, some of which contribute to therapeutic activity against tumors, whereas others drive undesired activity, such as immunosuppression or toxicity. We explored the theory that targeting of IL2 to CD8+ T cells, which are key antitumor effectors, could enhance its therapeutic index. To this aim, we developed AB248, a CD8 cis-targeted IL2 that demonstrates over 500-fold preference for CD8+ T cells over natural killer and regulatory T cells (Tregs), which may contribute to toxicity and immunosuppression, respectively.

CD8 cis-targeted IL-2 drives potent antiviral activity against hepatitis B virus.

CD8 T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8 T cell dysfunction showed that interleukin-2 (IL-2)-based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2's effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively.

Molecular and Clinicopathologic Characterization of Mismatch Repair-Deficient Endometrial Carcinoma Not Related to MLH1 Promoter Hypermethylation.

Universal tumor screening in endometrial carcinoma (EC) is increasingly adopted to identify individuals at risk of Lynch syndrome (LS). These cases involve mismatch repair-deficient (MMRd) EC without MLH1 promoter hypermethylation (PHM). LS is confirmed through the identification of germline MMR pathogenic variants (PV).

Functional recovery of wrist surgery with regional versus general anesthesia: a prospective observational study.

Purpose: Regional anesthesia may favour postoperative rehabilitation by inhibiting peripheral sensitization and secondary hyperalgesia. The literature on this subject is limited. In the present FUNCTION study, we sought to compare the functional recovery post orthopedic wrist surgery with regional versus general anesthesia.

Gynecological Cancer Survivors' Experiences of Dyspareunia and Factors Influencing Care-Seeking Behavior: A Qualitative Study.

Pain during sexual intercourse, also called dyspareunia, affects most women after treatment for gynecological cancer. Previous work adopted a biomedical approach to depict dyspareunia in this population, which provided a narrow perspective of this condition. Taking into account women's experiences of dyspareunia and the factors influencing their care-seeking behaviors would provide insight to improve care in the context of gynecological cancer.