Characterization of interleukin-2-initiated versus OKT3-initiated human tumor-infiltrating lymphocytes from glioblastoma multiforme: Growth characteristics, cytolytic activity, and cell phenotype View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1991-11

AUTHORS

Elizabeth A. Grimm, Janet M. Bruner, Judith Carinhas, Johannes A. Köppen, William G. Loudon, Laurie Owen-Schaub, Peter A. Steck, Richard P. Moser

ABSTRACT

Outgrowth of tumor-infiltrating lymphocytes (TIL) from the human primary brain tumor glioblastoma multiforme was achieved by OKT3 initiation (10 ng/ml), followed by sustained expansion by interleukin-2 (IL-2; 200 U/ml). Tumor-infiltrating lymphocyte (TIL) initiation by this process was performed in parallel with the standard “IL-2-only” method. Of ten tumors, seven yielded TIL in response to OKT3/IL-2, whereas only three of these seven grew after initiation with IL-2 alone. On the basis of cell doubling times, at least 60 doublings, resulting in (hypothetically) up to 1023 TIL from as few as 2 × 105 cells in tumor suspensions, could be achieved using OKT3/IL-2. OKT3-initiated TIL proliferated in culture for as long as 288 days, although senescence of some cultures occurred at as early as 73 days. Significant heterogeneity of lymphocytes infiltrating the fresh tumors and heterogeneity of resultant TIL phenotype and function were apparent, yet several common trends were noted. In all cases after OKT3 initiation, significant net growth was not apparent until approximately 14 days. In contrast, in the three samples that grew in response to IL-2 alone, log-phase growth was always observed earlier. During the early phase of the cultures, all TIL expressed some killing activity toward a broad spectrum of tumors, including the autologous tumor. No consistent preference of TIL for lysis of autologous tumor was observed. Glioblastoma multiforme TIL cultures contained a mixture of CD8+ and CD4+ cells, with few CD16+ or NKH-1+. Of the six TIL examined in detail for population phenotype in relationship to time in culture, four eventually became exclusively CD4+. Further analysis of these CD4+ TIL indicated that all were of the helper-inducer class, 4B4+ and 2H4−. Concurrent with the decline in CD8+ cells, a decline in the cytolytic activity of these TIL cultures occurred. Furthermore, in two TIL that remained CD8+, a decline in the cytolytic activity also occurred. Therefore, loss of killing activity was not merely a reflection of the major cell phenotype changes. These results indicate that the OKT3/IL-2 process provides an alternative to IL-2 alone for TIL initiation and growth, as well as providing a novel system for further analysis of tumorderived lymphocyte and accessory cell functional potential. More... »

PAGES

391-399

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf01741334

DOI

http://dx.doi.org/10.1007/bf01741334

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053568128

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/1848799


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44 IL-2 process
45 IL-2-only
46 NKH-1
47 OKT3 initiation
48 OKT3-initiated TIL
49 OKT3/IL-2
50 OKT3/IL-2 process
51 TIL cultures
52 TIL initiation
53 TIL phenotype
54 Tumor-infiltrating lymphocyte (TIL) initiation
55 accessory cell functional potential
56 activity
57 alternative
58 analysis
59 autologous tumor
60 basis
61 brain tumor glioblastoma multiforme
62 broad spectrum
63 cases
64 cell doubling time
65 cell functional potential
66 cell phenotype
67 cell phenotype changes
68 cells
69 changes
70 characteristics
71 characterization
72 class
73 common trend
74 consistent preference
75 contrast
76 culture
77 cytolytic activity
78 days
79 decline
80 detail
81 doubling
82 doubling time
83 early phase
84 expansion
85 fresh tumors
86 function
87 functional potential
88 glioblastoma multiforme
89 growth
90 growth characteristics
91 helper-inducer class
92 heterogeneity
93 human primary brain tumor glioblastoma multiforme
94 human tumor-infiltrating lymphocytes
95 initiation
96 interleukin-2
97 interleukin-2-initiated
98 log-phase growth
99 loss
100 lymphocyte (TIL) initiation
101 lymphocytes
102 lysis
103 major cell phenotype changes
104 method
105 mixture
106 mixture of CD8
107 multiforme
108 multiforme TIL cultures
109 net growth
110 novel system
111 outgrowth
112 parallel
113 phase
114 phenotype
115 phenotype changes
116 population phenotype
117 potential
118 preferences
119 primary brain tumor glioblastoma multiforme
120 process
121 reflection
122 relationship
123 response
124 resultant TIL phenotype
125 results
126 samples
127 senescence
128 significant heterogeneity
129 significant net growth
130 spectra
131 standards
132 suspension
133 sustained expansion
134 system
135 time
136 trends
137 tumor glioblastoma multiforme
138 tumor suspensions
139 tumor-infiltrating lymphocytes
140 tumors
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