RESUMO
Immunotherapy has become a mainstay of treatment for many cancers. Multiple immune checkpoint inhibitors have been used to treat malignancies, including anti-programed death-1 (PD1) and anti-cytotoxic T-lymphocyte-associated protein (anti-CTLA4). However, a significant percentage of patients develop resistance to these immunotherapy drugs. Therefore, novel strategies were developed to target other aspects of the immune response. Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule found on natural killer cells and activated T-cells which negatively regulates T-cell proliferation and function. LAG-3 inhibitors interact with LAG-3 ligands on the surface of T-cells to block T-regulatory (Treg) cell activity, suppress cytokine secretion and restore dysfunctional effector T-cells which subsequently attack and destroy cancer cells. This review reports the dermatologic side effects associated with LAG-3 inhibitors used in the treatment of melanomas. Using PRISMA 2022 guidelines, a comprehensive literature review of PubMed, Google Scholar, Embase, Cochrane, and Web of Science databases was conducted. Three studies were identified that demonstrated that the use of LAG-3 inhibitors, whether as a single agent or in combination with other immune checkpoint inhibitors, resulted in stomatitis, pruritus, rash, dry skin, erythema, and vitiligo. Further research is warranted to assess the cutaneous adverse events observed with LAG-3 inhibitors in treating melanoma and to identify populations most vulnerable to such side effects.
RESUMO
Though lion-tailed macaques are managed ex situ as an assurance population, little information is available on the relationship between behavior and reproductive physiology to ensure successful management and evaluate welfare. To facilitate social and reproductive management in a group of one male and three female lion-tailed macaques at Disney's Animal Kingdom®, we observed behaviors associated with dominance and reproduction, rated genital swellings, recorded menses, tracked ovarian cycles as determined by measurement of fecal immunoreactive progesterone (P4) and estradiol (E2), and monitored fecal cortisol (CORT). We analyzed the dominance hierarchy of females, compared hormone patterns of ovarian cycles with genital swellings and copulations relative to menses, and tested for correlations between hormones and behavior. The strength of the dominance hierarchy indicated moderate linearity, but relaxed after the dominant female received anxiolytic medications to reduce intraspecific aggression. Fecal P4 and E2 patterns revealed ovarian cycle lengths averaging 29.7 ± 0.8 days. The timing of single-day E2 peaks varied between and within females' cycles. However, on average, E2 peaks occurred 6-10 days after the first day of menses, with maximum genital swellings and copulations occurring slightly thereafter in uncontracepted females. Female-to-female aggression and sexual behaviors with the male were related to ovarian cycle phase, but correlations between behaviors and hormones varied between females. Initiated aggression was positively correlated with E2 in the dominant and mid-ranked females, while aggression received was positively correlated with P4 or negatively correlated with E2 in the mid-ranked and subordinate females. In one uncontracepted female, sexual behaviors with the male were negatively correlated to P4. CORT was positively correlated to aggression in the dominant and mid-ranked females and negatively correlated to grooming in the subordinate female. Results indicate observations of visual and behavioral cues can be used to track ovarian cycles and evaluate social dynamics and welfare in zoo-housed lion-tailed macaques.