Abstract
Clinical activity was observed in metastatic melanoma (MM) patients treated with ipilimumab (IPI) combined with fotemustine (FTM) in the phase II NIBIT-M1 study. Peripheral blood mononuclear cells (PBMCs) and serum were collected from MM patients at pre- and at weeks 12 and 24 post-treatment. A comprehensive phenotypic and functional immunomonitoring of circulating T cells, and the detection of soluble immunoregulatory molecules was carried out and correlated with clinical outcome. The frequency at baseline and along the treatment of circulating T central memory cells expressing activation/differentiation markers, such as CD3+CD4+CD45RO+BTLA+, CD3+CD4+4–1BB or Th17 lymphocytes correlated with the clinical outcome of MM patients. Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or −2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) = 33.6 mo for ULBP-1 and −2) from poor survivors (OS = 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3+CD4+CD45RO+BTLA+ or Th17 or CD3+CD4+4–1BB+ T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.
| Original language | English |
|---|---|
| Journal | OncoImmunology |
| Volume | 5 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 Feb 2016 |
| Externally published | Yes |
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Keywords
- Cytotoxic T-lymphocyte Antigen-4 (CTLA-4)
- Melanoma
- NKG2D ligands
- T cell subsets
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology
Cite this
Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study. / Maccalli, Cristina; Giannarelli, Diana; Capocefalo, Filippo; Pilla, Lorenzo; Fonsatti, Ester; Di Giacomo, Anna Maria; Parmiani, Giorgio; Maio, Michele.
In: OncoImmunology, Vol. 5, No. 2, 01.02.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study
AU - Maccalli, Cristina
AU - Giannarelli, Diana
AU - Capocefalo, Filippo
AU - Pilla, Lorenzo
AU - Fonsatti, Ester
AU - Di Giacomo, Anna Maria
AU - Parmiani, Giorgio
AU - Maio, Michele
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Clinical activity was observed in metastatic melanoma (MM) patients treated with ipilimumab (IPI) combined with fotemustine (FTM) in the phase II NIBIT-M1 study. Peripheral blood mononuclear cells (PBMCs) and serum were collected from MM patients at pre- and at weeks 12 and 24 post-treatment. A comprehensive phenotypic and functional immunomonitoring of circulating T cells, and the detection of soluble immunoregulatory molecules was carried out and correlated with clinical outcome. The frequency at baseline and along the treatment of circulating T central memory cells expressing activation/differentiation markers, such as CD3+CD4+CD45RO+BTLA+, CD3+CD4+4–1BB or Th17 lymphocytes correlated with the clinical outcome of MM patients. Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or −2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) = 33.6 mo for ULBP-1 and −2) from poor survivors (OS = 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3+CD4+CD45RO+BTLA+ or Th17 or CD3+CD4+4–1BB+ T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.
AB - Clinical activity was observed in metastatic melanoma (MM) patients treated with ipilimumab (IPI) combined with fotemustine (FTM) in the phase II NIBIT-M1 study. Peripheral blood mononuclear cells (PBMCs) and serum were collected from MM patients at pre- and at weeks 12 and 24 post-treatment. A comprehensive phenotypic and functional immunomonitoring of circulating T cells, and the detection of soluble immunoregulatory molecules was carried out and correlated with clinical outcome. The frequency at baseline and along the treatment of circulating T central memory cells expressing activation/differentiation markers, such as CD3+CD4+CD45RO+BTLA+, CD3+CD4+4–1BB or Th17 lymphocytes correlated with the clinical outcome of MM patients. Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or −2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) = 33.6 mo for ULBP-1 and −2) from poor survivors (OS = 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3+CD4+CD45RO+BTLA+ or Th17 or CD3+CD4+4–1BB+ T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.
KW - Cytotoxic T-lymphocyte Antigen-4 (CTLA-4)
KW - Melanoma
KW - NKG2D ligands
KW - T cell subsets
UR - http://www.scopus.com/inward/record.url?scp=84959378635&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959378635&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2015.1071007
DO - 10.1080/2162402X.2015.1071007
M3 - Article
AN - SCOPUS:84959378635
VL - 5
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 2
ER -