The Innate Immune System and the TRAIL-Bcl-XL Axis Mediate a Sex Bias in Lung Cancer and Confer a Therapeutic Vulnerability in Females.

There is a significant sex bias in lung cancer, with males showing increased mortality compared with females. A better mechanistic understanding of these differences could help identify therapeutic targets to personalize cancer therapies to each sex. After observing a clear sex bias in humanized mice, with male patient-derived xenograft lung tumors being more progressive and deadlier than female patient-derived xenograft lung tumors, we identified mouse tumor models of lung cancer with the same sex bias.

Restoration of CD4 T Cells during NAFLD without Modulation of the Hepatic Immunological Pattern Is Not Sufficient to Prevent HCC.

Predominant inflammatory immunological patterns as well as the depletion of CD4 T cells during nonalcoholic fatty liver disease (NAFLD) are reported to be associated with the progression of hepatocellular carcinoma (HCC). Here, we report that an LRP-1 agonistic peptide, SP16, when administered during advanced NAFLD progression, restored the depleted CD4 T cell population but did not significantly affect the inflammatory immunological pattern. This data suggests that restoration of CD4 T cells without modulation of the hepatic immunological pattern is not sufficient to prevent HCC.

Distinct hepatic immunological patterns are associated with the progression or inhibition of hepatocellular carcinoma.

To discover distinct immune responses promoting or inhibiting hepatocellular carcinoma (HCC), we perform a three-dimensional analysis of the immune cells, correlating immune cell types, interactions, and changes over time in an animal model displaying gender disparity in nonalcoholic fatty liver disease (NAFLD)-associated HCC. In response to a Western diet (WD), animals mount acute and chronic patterns of inflammatory cytokines, respectively. Tumor progression in males and females is associated with a predominant CD8 CD4, Th1 > Th17 > Th2, NKT > NK, M1 > M2 pattern in the liver.

Multifaceted functions of chronic inflammation in regulating tumor dormancy and relapse.

Inflammation is a double-edged sword exhibiting multifaceted functions. On one hand, it either induces tumor cell apoptosis, or establishes tumor dormancy by inhibiting tumor cell proliferation; on the other hand, it either facilitates the tumorigenesis process or reawakens dormant tumor cells, resulting in disease recurrences. Each outcome would depend on the balance between type I and type II inflammation as well as the duration of inflammation being acute or chronic.