[Lani]

hyaluronan is like glue in the space between cells and surrounds her2+ breast cancer cells in about 60% of her2+ tumors

translation of the rest:

Despite tremendous progress in cancer immunotherapy for solid tumors, clinical success of monoclonal antibody (MAb) therapy is often limited by poorly understood mechanisms associated with the tumor microenvironment (TME)--this is the area outside the tumor but adjacent to the tumor which serves as a home for the tumor, who we will compare to a fugitive mass murderer. The tumor(fugitive mass murderer) asks the microenvironment--mom, dad, grandma grandpa for food, warmth, blankets, drink and entertainment.

Mom, dad, grandpa and grandma besides sheltering and feeding the mass murderer/tumor also like the company of the tumor (mass murderer) and pass on wisdom, information on the location of the FBI/police, binoculars to look for lurking police/FBI outdoors, disguises and hope and other things that help it cope.Accumulation of hyaluronan (HA), a major component of the TME, occurs in many solid tumor types, and is associated with poor prognosis and treatment resistance in multiple malignancies.( It is a sticky, glue-like stuff leet's say it is a hedge-high moat or wall of supersticky cotton candy). In this study, we describe that a physical barrier associated with high levels of HA (HAhigh) in the TME restricts antibody and immune cell ( police and FBI who come to take away the fugitive mass murderer) access to tumors, suggesting a novel mechanism of in vivo resistance to MAb therapy.

We determined that ~60% of HER23+ primary breast tumors and ~40% of EGFR+ head and neck squamous cell carcinomas (those responsible for cancers of the mouth and other areas of the head and neck) are HAhigh, and hypothesized that HAhigh tumors may be refractory to MAb--monoclonal antibody) therapy.(monoclonal antibodies are smart-bombs, such as herceptin--if herceptin cannot get to the cancer cell because of the cotton candy moat it cannot stick to its her2 receptor or invite in killing immune cells like NK cells.) We found that the pericellular matrix(cottoncandy moat or hedge) produced by HAhigh tumor cells inhibited both natural killer (NK) immune cell access to tumor cells and antibody-dependent cell-mediated cytotoxicity (ADCC)--the process by which those killer cells kill the her2+ cells) in vitro.

Depletion of HA(cotton candy) by PEGPH20, a pegylated recombinant human PH20 hyaluronidase(enzyme that eats hyaluronon or cotton candy), resulted in increased NK cell access to HAhigh tumor cells, and greatly enhanced trastuzumab- or cetuximab-dependent ADCC in vitro. Furthermore, PEGPH20 treatment enhanced trastuzumab and NK cell access to HAhigh tumors, resulting in enhanced trastuzumab- and NK cell-mediated tumor growth inhibition in vivo. These results suggest that HAhigh matrix in vivo may form a barrier inhibiting access of both
MAb(herceptin) and NK cells(the cells attracted to come kill the her2+ breast cancer cells after being summoned by the herceptin"hey, guess what I found, a lovely her2+ breast cancer cell to kill and eat!" or alternatively, an FBI agent who is happy to have had
in informant call in but is frustrated because he cannot see thee location and whether the serial murderer is unarmed because the sticky cotton candy hedge obscures the murderer so the FBI agent cannot swoop in and "take him out!"), and that PEGPH20 treatment in combination with anti-cancer MAbs may be an effective adjunctive therapy for HAhigh tumors (both, acting together, serve to 1) act as an informant as to where the murderer is and 2) takes down the cotton candy hedge/moat so the FBI can come in for the kill)

I continue to believe you could utilize my chocolate, cherry and whipped cream system to fathom the information without my help. It might take a bit of practice, though.