Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

• Published in: The Journal of immunology (1950) Vol. 192; no. 3; pp. 1286 - 1293
• Main Authors: Arina, Ainhoa, Schreiber, Karin, Binder, David C., Karrison, Theodore, Liu, Rebecca B., Schreiber, Hans
• Format: Journal Article
• Language: English
• Published: 23-12-2013
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1202498

Myeloid-derived CD11b
+
Gr1
+
suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation
ex vivo
and can prevent the generation of T cell responses
in vivo
. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive
ex vivo
. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors
in vivo
revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that
in vivo
, myeloid immunosuppressive cells can suppress naive but not memory T cell responses.