NK1.1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours

Indrová, M; Šímová, Jana; Bieblová, Jana; Bubenı́k, Jan; Reiniš, Milan

doi:10.3892/or_00001072

Cited by 5 publications

(8 citation statements)

References 18 publications

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“…However, we did not observe significantly higher cytotoxicity of the spleen cells from the animals immunized with HHP-treated cells and this finding was in agreement with the results of immunization-challenge experiments. We did not see any significant differences between vaccination with HHP- or IR-treated tumor cells; both vaccinations inhibited TC-1 tumor growth, as expected and previously observed for the animals immunized with IR-treated cells ( 30 , 31 ) while the TRAMP-C2 tumor growth was not blocked by both of the vaccination protocols. It has been previously shown that TRAMP-C2 tumor cells are not immunogenic, unless their immunogenicity was increased by IFNγ treatment, inducing MHC class I cell surface expression ( 36 ).…”

Section: Discussionsupporting

confidence: 87%

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Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy

Mikyšková

Stĕpánek

Indrová

et al. 2015

International Journal of Oncology

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High hydrostatic pressure (HHP) has been shown to induce immunogenic cell death of cancer cells, facilitating their uptake by dendritic cells (DC) and subsequent presentation of tumor antigens. In the present study, we demonstrated immunogenicity of the HHP-treated tumor cells in mice. HHP was able to induce immunogenic cell death of both TC-1 and TRAMP-C2 tumor cells, representing murine models for human papilloma virus-associated tumors and prostate cancer, respectively. HHP-treated cells induced stronger immune responses in mice immunized with these tumor cells, documented by higher spleen cell cytotoxicity and increased IFNγ production as compared to irradiated tumor cells, accompanied by suppression of tumor growth in vivo in the case of TC-1 tumors, but not TRAMP-C2 tumors. Furthermore, HHP-treated cells were used for DC-based vaccine antigen pulsing. DC co-cultured with HHP-treated tumor cells and matured by a TLR 9 agonist exhibited higher cell surface expression of maturation markers and production of IL-12 and other cytokines, as compared to the DC pulsed with irradiated tumor cells. Immunization with DC cell-based vaccines pulsed with HHP-treated tumor cells induced high immune responses, detected by increased spleen cell cytotoxicity and elevated IFNγ production. The DC-based vaccine pulsed with HHP-treated tumor cells combined with docetaxel chemotherapy significantly inhibited growth of both TC-1 and TRAMP-C2 tumors. Our results indicate that DC-based vaccines pulsed with HHP-inactivated tumor cells can be a suitable tool for chemoimmunotherapy, particularly with regard to the findings that poorly immunogenic TRAMP-C2 tumors were susceptible to this treatment modality.

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Section: Discussionsupporting

confidence: 87%

“…Mice were twice immunized with 5×10 6 irradiated tumor cells in a three-week interval (s.c., irradiation dose was 150 Gy, HHP dose was 200 MPa) ( 13 , 30 , 31 ). For in vivo studies, 10 days after the second immunization, mice were challenged s.c. with corresponding tumor cells (TC-1, 5×10 4 ; TRAMP-C2, 1×10 6 cells/mouse).…”

Section: Methodsmentioning

confidence: 99%

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy

Mikyšková

Stĕpánek

Indrová

et al. 2015

International Journal of Oncology

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“…The B16F10 melanoma growth was significantly impaired, and lower number of tumor foci was detected in the lung using metastatic model of melanoma in the b+d-NK1.1neg strain compared to C57BL/6. This could be attributed to the upregulation of NKG2D in the novel strains and activation of cytotoxic effector cells that restrain the tumor growth (42,43). Similar effects were observed with MCB8 fibrosarcoma syngeneic to Balb/c.…”

Section: Discussionmentioning

confidence: 56%

“…Previously, we described the participation of activated NKT cells in the control of tumor growth at the early stages (45). The results of prophylactic immunization showed the distinct role of cell subsets in the development of immunity and the important role of NK cells (43).…”

Section: Discussionmentioning

confidence: 92%

Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors

Fišerová

Richter

Čapková

et al. 2016

International Journal of Oncology

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To elucidate the immunological mechanisms critical for tumor progression, we bred novel mouse strains, different in the NKC and H-2D domains. We used inbreeding to generate hybrids of Balb/c and C57BL/6 of stable H-2Db+d-NK1.1neg and H-2Db-d+NK1.1high phenotypes. We analyzed the growth of three established MHC class I-deficient tumor cell lines: TC-1/A9 tumor (HPV-associated) and B16F10 melanoma, both syngeneic to C57BL/6, and the MCB8 (3-methycholanthrene-induced tumor) syngeneic to Balb/c. Furthermore, we induced colorectal carcinoma by azoxymethane-DSS treatment to test the susceptibility to chemically-induced primary cancer. We found that the novel strains spontaneously regressed the tumor transplants syngeneic to both Balb/c (MCB8) and C57BL/6 (B16F10 and TC-1/A9) mice. The H2-Db+d-NK1.1neg, but not the H2-Db-d+NK1.1high strain was also highly resistant to chemically-induced colorectal cancer in comparison to the parental mice. The immune changes during TC-1/A9 cancer development involved an increase of the NK cell distribution in the peripheral blood and spleen along with higher expression of NKG2D activation antigen; this was in correlation with the time-dependent rise of cytotoxic activity in comparison to C57BL/6 mice. The TC-1/A9 cancer regression was accompanied by higher proportion of B cells in the spleen and B220+/CD86+ activated antigen-presenting B cells distributed in the lymphoid organs, as well as in the periphery. The changes in the T-cell population were represented mainly by the prevalence of T helper cells reflected by grown CD4/CD8 ratio, most prominent in the b+d-NK1.1neg strain. The results of the present study imply usefulness of the two novel mouse strains as an experimental model for further studies of tumor resistance mechanisms.

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“…In the Balb-high mice, the period of tumor growth was prolonged to 20 days, similarly to the Balb/c parental strain ( 4 ). In the prophylactic immunization experimental settings using irradiated TC-1/A9 tumor cells in C57BL/6 mice, a remarkable role of NK1.1-positive cells in the development of immunity was observed ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

The role of immune cell subpopulations in the growth and rejection of TC‑1/A9 tumors in novel mouse strains differing in the H2‑D haplotype and NKC domain

et al. 2018

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The present study aimed to elucidate the role of cluster of differentiation (CD)8+, CD4+, natural killer (NK), and myeloid (CD11b+) cells in the course of the growth and rejection of experimental major histocompatibility complex (MHC) class I-deficient, HPV16 E6/E7-associated TC-1/A9 tumors in mice. Stable mouse lines (F30) generated by inbreeding of Balb/c and C57BL/6 strains, which were characterized by H-2Db+d-NK1.1neg (B6-neg) and H-2Db-d+NK1.1high (Balb-high) phenotypes, were used for the present study. The novel strains spontaneously regressed tumors in 70–90% of cases. Ex vivo histological analysis of the tumor microenvironment in cryosections showed an indirect correlation between the growth of the transplanted tumor (progressor vs. regressor mice) and the proportion of immunocompetent cell infiltration in the tumors. The regressor mice exhibited a higher infiltration of tumors with CD4+ and CD8+ cells, and in Balb-high with NK cells as well, compared with the progressors. All tumor transplants also indicated a huge infiltration of CD11b+ cells, but this infiltration was not dependent on the stage of the TC-1/A9 tumor development. Depletion of individual cell subpopulations in vivo exhibited different effects on the tumor development in the two strains. Elimination of CD8-positive cells enhanced growth of TC-1/A9 tumor transplants in both hybrid stains, whereas CD4+ cell depletion affected rejection of TC-1/A9 tumors in the B6-neg mice only. Depletion of NK cells with anti-asialo GM1 antibody in the Balb-high strain led to enhancement of tumor growth, which was more pronounced after depletion of the NK1.1+ subpopulation. On the other hand, depletion of NK cells with anti-asialo GM1 in B6-neg mice did not affect the regression of TC-1/A9 tumor transplants, but increased the CD11b+ cell infiltration. In summary, these results indicate that co-operation of particular subsets of immunocompetent cells is essential for the rejection of TC-1/A9 tumor transplants. In B6-neg mice, the co-operative action of CD8+ and CD4+ cells is required, whereas in Balb-high mice, the synergy of CD8+ and NK1.1+ cells is of major importance.

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NK1.1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours

Cited by 5 publications

References 18 publications

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy

Dendritic cells pulsed with tumor cells killed by high hydrostatic pressure induce strong immune responses and display therapeutic effects both in murine TC-1 and TRAMP-C2 tumors when combined with docetaxel chemotherapy

Resistance of novel mouse strains different in MHC class I and the NKC domain to the development of experimental tumors

The role of immune cell subpopulations in the growth and rejection of TC‑1/A9 tumors in novel mouse strains differing in the H2‑D haplotype and NKC domain

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