Galunisertib plus neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer: a single-arm, phase 2 trial.

Background: TGF-β is an immunosuppressive cytokine that is upregulated in colorectal cancer. TGF-β blockade improved response to chemoradiotherapy in preclinical models of colorectal adenocarcinoma. We aimed to test the hypothesis that adding the TGF-β type I receptor kinase inhibitor galunisertib to neoadjuvant chemoradiotherapy would improve pathological complete response rates in patients with locally advanced rectal cancer.

Germinal center reactions in tertiary lymphoid structures associate with neoantigen burden, humoral immunity and long-term survivorship in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has traditionally been thought of as an immunologically quiescent tumor type presumably because of a relatively low tumor mutational burden (TMB) and poor responses to checkpoint blockade therapy. However, many PDAC tumors exhibit T cell inflamed phenotypes. The presence of tertiary lymphoid structures (TLS) has recently been shown to be predictive of checkpoint blockade response in melanomas and sarcomas, and are prognostic for survival in PDAC.

TGFβ suppresses CD8 T cell expression of CXCR3 and tumor trafficking.

Transforming growth factor beta (TGFβ) is a multipotent immunosuppressive cytokine. TGFβ excludes immune cells from tumors, and TGFβ inhibition improves the efficacy of cytotoxic and immune therapies. Using preclinical colorectal cancer models in cell type-conditional TGFβ receptor I (ALK5) knockout mice, we interrogate this mechanism.

Blockade of fibroblast activation protein in combination with radiation treatment in murine models of pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma with a poor lymphocyte infiltrate, in part driven by cancer-associated fibroblasts (CAFs). CAFs, which express fibroblast activation protein (FAP), contribute to immune escape via exclusion of anti-tumor CD8+ T cells from cancer cells, upregulation of immune checkpoint ligand expression, immunosuppressive cytokine production, and polarization of tumor infiltrating inflammatory cells. FAP is a post-proline peptidase selectively expressed during tissue remodeling and repair, such as with wound healing, and in the tumor microenvironment by cancer-associated fibroblasts.

Readability of hospice materials to prepare families for caregiving at the time of death.

Many health care materials are not written at levels that can be understood by most lay people. In this descriptive study, we examined the readability of documents used by hospices to prepare families for caregiving at the time of death. We used two common formulae to examine the documents.

Does sharing research data with participating hospices affect practice?

Background: The research question guiding this study was, "Does receiving individualized feedback about the findings of a research study that the hospice participated in affect clinical practice?" Three issues were examined: (1) Did anyone at the hospice recall receiving the research results? (2) Were the findings shared with the hospice staff? and (3) Did the findings influence clinical practice in the hospice?

Methods: The sample was 170 hospices that participated in a previous study examining the written materials used by hospices to prepare families for death. Participating hospices were sent individualized feedback concerning the signs of impending death and types of information that were present in their hospice's materials. Approximately 1 year later, participating hospices received a follow-up survey.