NorthWest Biotherapeutics Inc (NWBO)

[Doc logic]

Doktornolittle,

There are 2 main types of macrophage characteization. These are known as M1 and M2. M1 type macrophages enhance immune response while M2 macrophages help apply the brakes and are immunosuppressive. They carry the PD-1 markers that help shut down the helper and hunter T-cell responses. Cancer can respond to attack by calling in these types of immunosupressive macrophages (M2). Properly activated DCs can apparently control these M2s with cytokine signaling in at least the mesenchymal subtype. This is consistent with higher numbers of T-cells present before treatment begins due to more targets that mesenchymal subtype presents. This is also why treatment spacing improvements in L and Direct have and should offer some positive surprises in the open label trials and Phase 2 Direct trial. Checkpoint inhibitors will also help weaker immune responses from other (less mesenchymal) subtypes to continue to progress even as the genetic changes to these tumors after chemo/radiation make them more mesenchymal like at recurrence. Best wishes.