584 Therapeutic vascular normalization to promote tumor-associated tertiary lymphoid structures

Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.

Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLSs...

Tumor-Associated Tertiary Lymphoid Structures: Gene-Expression Profiling and Their Bioengineering

Tertiary lymphoid structures (TLSs) have been identified in the parenchyma and/or in the peripheral margins of human solid tumors. Uncovering the functional nature of these structures is the subject of much intensive investigation. Studies have shown a direct correlation of the presence of human tumor-localized TLS and better patient outcome (e.g., increase in overall survival) in certain solid...

Lymphocytes in Autoimmune Diabetes Pancreas Promote Selection of B Tertiary Lymphoid Structures in the

Tertiary lymphoid structures in the pancreas promote selection of B lymphocytes in autoimmune diabetes.

Autoimmune diabetes occurs when invading lymphocytes destroy insulin-producing beta cells in pancreatic islets. The role of lymphocytic aggregates at this inflammatory site is not understood. We find that B and T lymphocytes attacking islets in NOD mice organize into lymphoid structures with germinal centers. Analysis of BCR L chain genes was used to investigate selection of B lymphocytes in th...

Tumor vascular normalization as a strategy to potentiate effectiveness of therapeutic vaccines

Purpose The effectiveness of cancer immunotherapy can be compromised when immune cells cannot penetrate the tumor. We hypothesize that combining an antiangiogenic tyrosine kinase inhibitor (TKI) with a cancer vaccine can increase antitumor response by targeting 3 elements of the tumor microenvironment (TME): (a) tumor endothelial cells, which can lead to vascular normalization; (b) tumor cells,...