Abstract Book 2010 - CIMT Annual Meeting

034 Guidoboni | Immune monitoring
Changes of immune cell infiltrates induced by dendritic cell
vaccination in melanoma patients‘ tumor tissues:
an immunohistochemical study
Massimo Guidoboni 1 , Laura Ridolfi 1 , Annamaria Granato 1 , Massimiliano Petrini 1 , Laura
Fiammenghi 1 , Valentina Ancarani 1 , Elena Pancisi 1 , Linda Valmorri 1 , Angela Riccobon 1 ,
Roberta Gafà 2 , Giovanni Lanza 2 , Dino Amadori 3 , Ruggero Ridolfi 1
1 Immunotherapy and Somatic Cell Therapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei
Tumori, Meldola (FC), Italy
2 Department of Pathology, University of Ferrara, Italy
3 Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola (FC), Italy
We have been treated more than 40 patients in a
phase I/II study of therapeutic vaccination using
DC pulsed with autologous tumor lysate or homogenate
in advanced melanoma. Objective responses
are observed in a limited number of patients, clinical
responses rates as evaluated by classical responses
criteria are still disappointing, and we are not able
to identify patients who will benefit from DC vaccination.
Spontaneous and vaccine-induced antitumor
immune responses have been extensively characterized
in peripheral circulating compartment,
and in some cases this approach predicted clinical
response to immunotherapy; however, we do not
know whether this translate into efficient immune
cell recruiting in all tumor sites. To shed light on
changes induced by DC vaccine on the composition
of immune effectors in tumor sites, we evaluated
tumor infiltrating lymphocytes (TILs) in 12
tumor biopsies taken from 4 patients before and at
different times after DC vaccination for metastatic
melanoma. Two patients showed complete clinical
responses (CR) after at least 6 courses of vaccine.
In one of these patients DC vaccination induced
huge amount of CD8+ activated cytotoxic lymphocytes
(24,89 CD8+ TILs/100 melanoma cells)
in one tumor site compared to prevaccine biopsy;
however, negligible levels of CD8+ TILs together
with considerable amount of CD4+ cells were found
in one other relapsed site, suggesting that immune
escape had occurred. The other patient showing
CR underwent relapse and progressive surgical de-
bulking of metachronous localizations led to surgical
CR still lasting. Tumor biopsies taken after
vaccination showed lower amount of CD8+ TILs
than those collected before (2,13 and 1,38 vs 8,44
CD8+ TILs/100 tumor cells), showing that complete
surgical removal of „immune escaped“ lesions
may lead to persistent CR in patients with good
clinical status. One patient undergone progression
after Ipilimumab failure showed considerable
levels of CD8+ TILs. After 9 courses of DC vaccine
with stable disease (SD), she relapsed and progressing
lesion was removed, with decreased amount of
tumor infiltrating CD8+ lymphocytes in this tumor
site. The last patient has been vaccinated for 4 years
with still lasting SD, and further tumor biopsies
were taken to prepare additional doses of vaccine.
Treatment induced lower increase of CD8+ TILs
in postvaccine biopsies than those observed in the
other patients (3,28 and 1,93 vs 1,12 CD8+ TILs/100
tumor cells), suggesting that lower immune pressure
might allow to reach an equilibrium between
immune system and tumor which slow occurrence
of immune escape. Although performed on a
limited number of cases, this study firstly explored
the possible role for „tissue immune monitoring“ in
the clinical setting and strongly indicate its use to
direct clinical decision in multimodal therapeutic
approach.
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