Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin

Steerenberg, P. A.; Jong, Wim H. de; Geerse, E.; Aleva, B. J.; Besselink, C. M. L. T.; Rens, B.T.T.M. van; Rutten, Victor P.M.G.; Poels, L. G.; Scheper, Rik J.; Otter, W. Den; Ruitenberg, E. J.

doi:10.1007/bf01754205

Cited by 6 publications

(12 citation statements)

References 39 publications

(30 reference statements)

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“…This cure is followed by the induction of immunity to a second challenge with line 10 tumour cells [14,17,31,41]. More recently this immunity to line 10 was demonstrated within 1 week after bacillus Calmette-Guérin (BCG) treatment [35]. This was substantiated by the immunohistological observation that there is an ongoing immune response in this early phase in the non-treated tumours [36].…”

Section: Introductionmentioning

confidence: 92%

“…The single-colour staining method was performed as described previously [35]. The mAbs were used in the following dilutions: MSgp9, 10TL1, 10TL40, 10TL43 and MSgp4, 1 : 10; M305, 1 : 50; CT5, CT7, T188, and 31D2, 1 : 200; 25E3 and CT6, 1:500.…”

Section: Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

“…Cells from spleen, lymph nodes and tumour were collected as described previously [35]. To enumerate the viable cells suspensions were counted with the trypan blue (0.5%) exclusion method and adjusted to the desired concentrations.…”

Section: Animalsmentioning

confidence: 99%

“…Furthermore, it was demonstrated that BCG induced in the tumour an increased number of tumour-infiltrating leukocytes expressing MHC class II antigen. By single-colour flow cytofluorometry, this MHC class 1I antigen expression was found on B cells in the regional lymph node, and on T cells in the tumour [35]. These aspects were investigated in Single: in single-colour flow cytofluorometry the cells were stained with mAb according to the indirect standard immunofluorescence procedure (FITC) b Two-colour: in the two-colour flow cytofluorometry the cells were stained with indirect staining procedures with anti-L2C or anti-(pan T cell) and PE-conjugated rat anti-(mouse IgG) and subsequently stained with FITC-conjugated anti-(MHC class II antigen) mAb ° L2C + and L2C-: L2C-leukemia-positive or -negative, respectively, for MHC class II antigen expression more detail in the present study.…”

Section: Introductionmentioning

confidence: 96%

“…Previously we found [35] that intracutaneous or intratumoral injection of BCG induces a more than tenfold increase of cells in regional lymph nodes, and an increase of MHC class II expression in these lymph nodes. Furthermore, it was demonstrated that BCG induced in the tumour an increased number of tumour-infiltrating leukocytes expressing MHC class II antigen.…”

Section: Introductionmentioning

confidence: 98%

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Major histocompatibility complex class II antigen expression on leucocyte subpopulations in the draining lymph node and tumour in the early phase of bacillus-Calmette-Guérin-induced tumour regression

Steerenberg

Jong

Geerse

et al. 1991

Cancer Immunol Immunother

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We investigated the cellular composition and the major histocompatibility complex (MHC) class II antigen expression in the draining lymph node and the tumour during potentiation of the immune response by intralesional bacillus Calmette-Guérin (BCG) administration in the line 10 hepatocellular carcinoma in the strain 2 guinea-pig. Five days after its injection BCG induced a ninefold increase in the number of draining lymph node cells and an increased MHC class II expression. This increased MHC class II expression was mostly due to the selective increase of B cells in the lymph nodes, and to a lesser extent to the increase of T cells expressing MHC class II antigens. Taking into account this nine-fold increase, intralesional treatment of BCG increased considerably the number of T helper/inducer (anti-CT7) and T suppressor/cytotoxic (anti-CT6) lymph node cells expressing MHC class II antigen. The percentage of tumour-infiltrating T cells expressing MHC class II antigen in the tumour was higher than the percentage of T cells in the regional draining lymph node of non-treated guinea-pigs, indicating the presence of activated T cells in the tumour. After treatment with BCG no further increase in MHC class II expression was measured in the tumour, nor was any phenotypical change of the tumour-infiltrating T cells found. In conclusion, with the use of two-colour flow cytofluorometry we have shown that the potentiation of the already existing immune response to line 10 is accompanied by a considerable increase in T helper/inducer, T suppressor/cytotoxic cells and MHC class II antigen in the regional lymph node. Whether this is essential for the potentiation of the immune response causing tumour regression and long-lasting immunity is a subject for further study.

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Section: Introductionmentioning

confidence: 92%

Section: Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 98%

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Major histocompatibility complex class II antigen expression on leucocyte subpopulations in the draining lymph node and tumour in the early phase of bacillus-Calmette-Guérin-induced tumour regression

Steerenberg

Jong

Geerse

et al. 1991

Cancer Immunol Immunother

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Polyethylene‐glycol‐modified interleukin‐2 is superior to interleukin‐2 in locoregional immunotherapy of established guinea‐pig tumors

Mattijssen¹,

Balemans

Steerenberg

et al. 1992

Intl Journal of Cancer

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Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy.

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Specific tumor memory induced by polyethylene-glycol-modified interleukin-2 requires both helper and cytotoxic T cells

et al. 1995

Cancer Immunol Immunother

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Local polyethylene-glycol (PEG)-modified interleukin-2 (IL-2) immunotherapy of the guinea pig Line 10 (L10) tumor was previously demonstrated to evoke long-lasting systemic immunity after cure of the tumor and metastases. T cells, most likely the helper T cell subpopulation, were demonstrated to be crucial to the antitumor effects. Here we show that systemic immunity is induced within 7 days after the start of PEG-IL-2 therapy, indicating a rapid systemic priming of L10-specific T cells. No in vitro cytotoxic activity was detected in cell suspensions obtained from the primary tumor site, the regional lymph node or the spleen when isolated during (days 21 and 28) intratumoral treatment with 200,000 IU PEG-IL-2. These data confirm our earlier results obtained with 60,000 IU PEG-IL-2. Moreover, no cytolytic activity was observed in the chromium-release assay after in vitro restimulation with irradiated tumor cells. Specific L10 immunity can be transferred using spleen cell suspensions. Depletion of such a suspension of helper T cells resulted in rejection of the primary tumor in two out of four animals, but all the guinea pigs developed lymph node metastases. Removal of the cytotoxic/suppressor phenotype caused rejection of the dermal tumor in four of eight guinea pigs, but the capacity to prevent lymph node metastases was retained in all animals. Thus, depletion of either subtype reduces, but does not abrogate, the capacity to transfer L10 immunity with spleen cells. In conclusion, our data suggest that tumor cell killing through direct T cell cytotoxicity is not the main mode of action in PEG-IL-2-induced L10 tumor regression. PEG-IL-2 therapy induces early systemic immunity, resulting in rejection of a distant tumor, and the transfer of this immunity depends mainly on the presence of helper T cells, although cytotoxic T cells may also play a role.

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Major histocompatibility complex class II antigen expression during potentiation of line-10 tumor immunity after intralesional administration of bacillus Calmette-Guérin

Cited by 6 publications

References 39 publications

Major histocompatibility complex class II antigen expression on leucocyte subpopulations in the draining lymph node and tumour in the early phase of bacillus-Calmette-Guérin-induced tumour regression

Major histocompatibility complex class II antigen expression on leucocyte subpopulations in the draining lymph node and tumour in the early phase of bacillus-Calmette-Guérin-induced tumour regression

Polyethylene‐glycol‐modified interleukin‐2 is superior to interleukin‐2 in locoregional immunotherapy of established guinea‐pig tumors

Specific tumor memory induced by polyethylene-glycol-modified interleukin-2 requires both helper and cytotoxic T cells

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