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Immunosuppression in inflammatory melanoma: can it be resisted by adoptively transferred T cells?
Author(s) -
AuphanAnezin Nathalie,
Verdeil Grégory,
Grange Magali,
Soudja Saïdi M.,
Wehbe Maria,
Buferne Michel,
Mas Amandine,
SchmittVerhulst AnneMarie
Publication year - 2013
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12056
Subject(s) - melanoma , adoptive cell transfer , cancer research , immunology , medicine , immunosuppression , tumor microenvironment , immunotherapy , inflammation , t cell , immune system
Summary Discovery of tumor antigen ( TA ) recognized by autologous T cells ( TC s) in patients with melanoma has led to clinical protocols using either vaccination or adoptive transfer of TA ‐specific TC s. However, efficacy of these treatments has been hampered by inhibitory effects exerted on tumor‐infiltrating TC s by tumor‐intrinsic mediators or by recruitment of immunosuppressive cells. A mouse model of autochthonous melanoma recapitulates some aspects of inflammatory melanoma development in patients. These include a systemic T h2‐/ T h17‐oriented chronic inflammation, recruitment of immunosuppressive myeloid cells and acquisition by tumor‐infiltrating TC s of an ‘exhausted’ phenotype characterized by expression of multiple inhibitory receptors including programmed death‐1, also expressed on patients' melanoma‐infiltrating TC s. Rather than using extracellular blocking reagents to inhibitory surface molecules on TC s, we sought to dampen negative signaling exerted on them. Adoptively transferred TC s presenting increased cytokine receptor signaling due to expression of an active Stat5 transcription factor were efficient at inducing melanoma regression in the preclinical melanoma model. These transferred TC s thrived and retained expression of effector molecules in the melanoma microenvironment, defining a protocol endowing TC s with the ability to resist melanoma‐induced immunosuppression.