Autophagy

A very key highlight of Craig's presentation at the Noble Financial Capital Markets' Eighth Annual Equity Conference were his reference to and comments on:

• Work by Michaud et al, presented in Science Magazine (and reported by Genetic Engineering & Biotechnology News). See here, here and here.

This independent, peer reviewed work shows (confirms) what Craig and his team have been saying for 10-12 years -- that autophagy generates anti-tumor immunity, which is t-cell independent.

The GEN article provides a nice synopsis of Michaud et al. work: "Autophagy of chemotherapy-treated dying cancer cells is necessary for triggering additional anticancer immune responses against remaining tumor cells..."

The abstract of the Science Magazine article is here: "Autophagy can promote the survival of tumor cells through nutrients recovered from degrading and recycling damaged organelles. How this mechanism can stimulate or limit the immune system's attack on tumor cells has not been well understood. Michaud et al. show that in mice, chemotherapy-induced autophagy causes the release of adenosine 5′-triphosphate (ATP) from tumor cells, thereby stimulating antitumor immune responses."

The abstract of Michaud et al's work is here: "Antineoplastic chemotherapies are particularly efficient when they elicit immunogenic cell death, thus provoking an anticancer immune response. Here we demonstrate that autophagy, which is often disabled in cancer, is dispensable for chemotherapy-induced cell death but required for its immunogenicity. In response to chemotherapy, autophagy-competent, but not autophagy-deficient, cancers attracted dendritic cells and T lymphocytes into the tumor bed. Suppression of autophagy inhibited the release of adenosine triphosphate (ATP) from dying tumor cells. Conversely, inhibition of extracellular ATP-degrading enzymes increased pericellular ATP in autophagy-deficient tumors, reestablished the recruitment of immune cells, and restored chemotherapeutic responses but only in immunocompetent hosts. Thus, autophagy is essential for the immunogenic release of ATP from dying cells, and increased extracellular ATP concentrations improve the efficacy of antineoplastic chemotherapies when autophagy is disabled."