Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042.
BACKGROUND
Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL).


METHODS
For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patient's objective response at the end of the study.


RESULTS
Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit.


CONCLUSIONS
These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response.


BACKGROUND
The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693.
Transgene S,A,, Boulevard Gonthier d'Andernach, Parc d'Innovation, 67405 Cedex Illkirch Graffenstaden, France. rooke@transgene.fr.
Nathalie
N
Accart
Mirjana
M
Urosevic-Maiwald
Reinhard
R
Dummer
Vincent
V
Bataille
Nadine
N
Kehrer
Cristina
C
Niculescu
Jean-Marc
JM
Limacher
Marie-Pierre
MP
Chenard
Jean-Yves
JY
Bonnefoy
Ronald
R
Rooke
D018450:Disease Progression; D005822:Genetic Vectors / Q000008:administration & dosage*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000276:immunology*