caa a22 4500 469074310 CHVBK 20180323132931.0 cr unu---uuuuu 170328e19920701xx s 000 0 eng 10.1007/BF01741792 doi (NATIONALLICENCE)springer-10.1007/BF01741792 Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype [Elektronische Daten] [Licia Rivoltini, Flavio Arienti, Attilio Orazi, Graziella Cefalo, Marco Gasparini, Carlo Gambacorti-Passerini, Franca Fossati-Bellani, Giorgio Parmiani] Summary: Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histo-type (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific” lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor α (TNFα) or interferon γ, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR γ/δ cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogeneic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNFα and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor β (TGFβ). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours. Springer-Verlag, 1992 Tumour-infiltrating lymphocytes nationallicence Paediatric tumours nationallicence Cytokines nationallicence TGFβ nationallicence Rivoltini Licia Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut Arienti Flavio Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut Orazi Attilio Division of Pathology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut Cefalo Graziella Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut Gasparini Marco Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut Gambacorti-Passerini Carlo Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut Fossati-Bellani Franca Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut Parmiani Giorgio Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut Cancer Immunology, Immunotherapy Springer-Verlag 34/4(1992-07-01), 241-251 0340-7004 34:4<241 1992 34 262 https://doi.org/10.1007/BF01741792 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741792 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rivoltini Licia Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut NATIONALLICENCE 700 1- Arienti Flavio Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut NATIONALLICENCE 700 1- Orazi Attilio Division of Pathology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut NATIONALLICENCE 700 1- Cefalo Graziella Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut NATIONALLICENCE 700 1- Gasparini Marco Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut NATIONALLICENCE 700 1- Gambacorti-Passerini Carlo Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut NATIONALLICENCE 700 1- Fossati-Bellani Franca Division of Paediatric Oncology, Istituto Nazionale Tumori, I-20 133, Milan, Italy aut NATIONALLICENCE 700 1- Parmiani Giorgio Division of Experimental Oncology D, Istituto Nazionale Tumori, Via Venezian 1, I-20 133, Milano, Italy aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 34/4(1992-07-01), 241-251 0340-7004 34:4<241 1992 34 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer