Patients with triple-negative breast cancer (TNBC) have a poor prognosis, partly because of the absence of targeted therapies. Recognition of the key role of immune responses against cancer has allowed the advent of immunotherapy, focused on the inhibition of negative immune checkpoints, such as CTLA-4. CTLA-4 is also expressed in some cancer cells, but its activity in tumor cells is not completely understood. Thus, the aim of the present work was to determine the biological landscape and functions of CTLA-4 expressed in TNBC cells through preclinical and in silico analysis. Exploration of CTLA-4 by immunohistochemistry in 50 TNBC tumors revealed membrane and cytoplasmic expression at different intensities. Preclinical experiments, using TNBC cell lines, showed that stimulation of CTLA-4 with CD80 enhances activation of the ERK1/2 signaling pathway, while CTLA-4 blockade by Ipilimumab induces the activation of AKT and reduces cell proliferation in vitro. We then developed an analytic pipeline to define the effects of CTLA-4 in available public data that allowed us to identify four distinct tumor clusters associated with CTLA-4 activation, which are characterized by enrichment of distinctive pathways associated with cell adhesion, MAPK signaling, TGF-ß, VEGF, TNF-α, drug metabolism, ion and amino acid transport, and KRAS signaling, among others. In addition, blockade of CTLA-4 induced increased secretion of IL-2 by tumor cells, suggesting that the receptor regulates cellular functions that may impact the immune microenvironment. This is relevant because a deep characterization of immune infiltrate, conducted using public data to estimate the abundancies of immune-cell types, showed that CTLA-4-activated-like tumors present a conditional immune state similar to an escape phenotype exploited by cancer cells. Finally, by interrogating transcriptional predictors of immunotherapy response, we defined that CTLA-4 activation correlates with high immune scores related to good clinical predicted responses to anti-CTLA-4 therapy. This work sheds new light on the roles of activated CLTA-4 in the tumor compartment and suggests an important interplay between tumor CLTA-4-activated portraits and immune-infiltrating cell populations.

Introduction: There are few studies regarding the clinical characteristics of Miller Fisher syndrome (MFS) in the Latin-American population. Methods: A retrospective analysis was made of the clinical characteristics, neurophysiology, treatment and prognosis of MFS patients between 1995 and 2005. Results: Nineteen MFS cases were documented, 12 of which did not receive immunosuppressive therapy. In both groups, the mean age was 36 years, 84% were male; onset in spring and fall was also predominant (73%), and antecedents of respiratory disease were found (79%). The mean duration of infectious symptoms was 7 days (1–11 days), and the mean interval between the onset of the infection and neurological symptoms was 7 days (1–30 days). The principal sign of onset was diplopia (63%). The mean delay between the onset of neurological symptoms and the beginning of recovery from ataxia, ophthalmoplegia and areflexia was 10 (1–30 days), 11 (1–30 days) and 14 (4–45 days) days, respectively, and the mean delay of the disappearance of ataxia, ophthalmoplegia and areflexia was 35 (10–121 days), 93 (18–244 days) and 64 (10–650 days) days, respectively. There was no significant difference between the group that received immunosuppression and the one that did not. Discussion: The natural course of MSF is characterized by excellent recovery; there were no differences between the two groups.

Background An up-to-date analysis of gastric cancer mortality among Hispanic/Latino populations is required for estimating disease burden and assessing the effectiveness of clinical and preventive strategies. Methods We retrieved gastric cancer deaths between 1997 and 2017 (as available) from the Surveillance, Epidemiology, and End Results Program (United States Hispanics) and the World Health Organization databases (Puerto Rico, 16 Latin American and Caribbean countries). Joinpoint regression analysis was used to examine trends in agestandardized mortality rates (ASMR; per 100 000 person-years) and calculate average annual percent changes (AAPCs) by country (or territory), age group (25-49 and >= 50 years), and sex. Trends were compared to assess slope parallelism. Findings In 2017, Chile (31.8), Colombia (24.3) and Costa Rica (24.3) had the highest ASMR of gastric cancer for men, while Guatemala (17.2), Peru (13.5), and Costa Rica (13.3) had the highest ASMR for women. Small-to-moderate mortality declines (AAPCs ranged -4 to -0.5%) were observed between 1997 and 2017. In almost all countries, trends decreased among individuals aged >= 50 years. However, age-specific trends were not parallel (p-values <0.05) in Brazil, Colombia, Mexico, the United States, and Venezuela for both men and women, and in five additional countries for only women; with a few countries showing stable or slightly increasing trends for individuals aged 25-49 years. Interpretation Overall gastric cancer mortality rates in Hispanics/Latinos declined in the last two decades. However, there was a notable variation in trends by country, sex, and age group. Continued and targeted prevention efforts are needed to reduce the disease burden in these vulnerable populations. Copyright (C) 2022 The Authors. Published by Elsevier Ltd.