Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment Melanoma Jim Breitfeller

Thomas F. Gajewski
Author's Affiliation: Departments of Pathology and Medicine, University of Chicago, Chicago, Illinois

Requests for reprints: Thomas F. Gajewski, University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL 60637. Phone: 773-702-4601; Fax: 773-702-3163; E-mail: tgajewsk@medicine.bsd.uchicago.edu.



"Metastatic melanoma tumors seem to be deficient in expression of B7-1 and B7-2 (16), which are important costimulatory factors for full T-cell activation (17). Stimulation through the T-cell antigen receptor without B7 costimulation has been shown to induce a hyporesponsive state termed anergy (18, 19). In support of this possibility, we recently have observed in a mouse model that a T-cell hyporesponsive state consistent with anergy occurs in mice bearing B7-negative tumors (20). In this situation, tumor rejection indeed can occur when B7-1 is transfected into the tumor cells, an observation that has been reported by multiple laboratories in other model systems (21, 22)."

In my case we stimulated the B7 receptor with anti-CTLA-4 Blockage, in the present of the antigen presenting cell (APC) that activated the CD4+T-cell it was allowed to propagate for 49 days (43 days gave the maximum propagation. Than we added the IL-2 therapy which we know by experiments the done by Rosenberg that Il-2 is able to pass throught the Tumor's microenvironment.

In 1980, Dr. Steven A. Roesnberg and colleagues discovered novel novel method for killing metastatic cancer cells. They took lymphoid cells and exposed them to interluekin-2 (IL-2).These cells were able to lyse the tumor cells and kill them. The were a different population than the Natural Killer cells. They coined the term “Lymphokine-activated killer cells” (LAK) for short.

Also, When patients do IL-2 therapy, they have side-effect Known as cell leakage. Il-2 makes the cell wall porous.

With the tumor cells walls compromised and with the activated effector T cells, the assualt on the tumors begin.

At Least, that is the way I envision it. There is probably a lot more going on behind the scenes.

Jimmy B