<i>In vivo</i> H‐2K and H‐2D antigen expression In two allogeneic mouse tumours of low immunogenicity

Ashley, Michael P.; Kotlarski, Ieva

doi:10.1038/icb.1987.36

Cited by 8 publications

(4 citation statements)

References 17 publications

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“…MHC-I expression acts as dominant tumour antigen in our model as evidenced by the following observations: (1) when MHC-I expression was up-regulated on B16 melanoma cells by pre-incubation with IFN-γ, the adaptive immune response was stronger and associated with alloreactive antibody production and the inhibition of tumour progression (Figure 2); (2) injection of EL-4 lymphoma (H-2K b ) and MC38 colon cancer cells (H-2K b ) which express normal levels of MHC-I antigens provoked strong alloreactive immune response and were rejected by the allogenic hosts (Figure 2). These results are in line with previous studies demonstrating that low MHC-I antigen expression is associated with tumour growth in allogenic mice [14,15,19,20]. Recent clinical trials in pre-treated small-cell lung cancer (SCLC) patients demonstrated that checkpoint blockade therapies resulted in response rates in only 10% and 25% of patients, which was lower compared to non-small-cell lung cancer (NSCLC) [10,11,12,21].…”

Section: Discussionsupporting

confidence: 93%

“…B16 melanoma injection in allogeneic Balb/c mice, pulmonary metastases were observed from day 7 onwards resulting in 100% animal death. We demonstrated that tumour progression was driven by low expression of MHC-I resulting in insufficient anti-cancer adaptive immune responses [15,16,17,18,19,20], as evidenced by a delayed/decreased alloreactive antibody response. MHC-I expression acts as dominant tumour antigen in our model as evidenced by the following observations: (1) when MHC-I expression was up-regulated on B16 melanoma cells by pre-incubation with IFN-γ, the adaptive immune response was stronger and associated with alloreactive antibody production and the inhibition of tumour progression (Figure 2); (2) injection of EL-4 lymphoma (H-2K b ) and MC38 colon cancer cells (H-2K b ) which express normal levels of MHC-I antigens provoked strong alloreactive immune response and were rejected by the allogenic hosts (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

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Improved Anti-Tumour Adaptive Immunity Can Overcome the Melanoma Immunosuppressive Tumour Microenvironment

Dang

Waer

Sprangers

et al. 2019

Cancers

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Clinical benefits obtained from checkpoint blockade regimens demonstrate the importance of overcoming the immunosuppressive tumour microenvironment (TME) in cancer immunotherapy. Intravenous (i.v.) injection of B16 melanoma cells (H-2Kb) leads to lethal disseminated pulmonary metastasis in Balb/c recipients (H-2Kd). This lack of immune control is related to low major histocompatibility complex (MHC) expression on B16 cells which is associated with delayed and decreased anti-tumour adaptive immune responses (e.g., alloantibody formation) as: (i) other tumour types with normal H-2Kb expression are rejected with concomitant antibody production; (ii) preincubation of B16 with IFN-gamma to upregulate H-2Kb expression resulted in improved antibody production and anti-tumour activity. The delayed/decreased anti-tumour adaptive immune responses induced by B16 inoculation is not able to interrupt progression of primary metastases, while it is able to effectively eliminate secondary inoculated subcutaneously (s.c.) B16 cells from progression. This is due to the presence of an immunosuppressive TME within the primary metastases characterized by increased regulatory T cells (Tregs) and an increased T helper cells (Th) 2/1 profile. These tumour-induced immunosuppressive T cell populations are counteracted by improved adaptive immunity via active and passive immunization, resulting in effective elimination of the TME, destruction of the metastatic tumour and a reversal of Th2/1 profile in a time-sensitive manner. Thus, we here demonstrate that the TME is not irreversible and adaptive immunity is able to eradicate established solid tumour and its immunosuppressive TME. This study will help design treatments to overcome the immunosuppressive effect of the TME and improve efficacy of cancer immunotherapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Improved Anti-Tumour Adaptive Immunity Can Overcome the Melanoma Immunosuppressive Tumour Microenvironment

Dang

Waer

Sprangers

et al. 2019

Cancers

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“…Eisenbaeh and coworkers (23) attributed the failure of allogeneic mice to reject Lewis lung carcinoma to a selective deficiency in the expression of H-2K'' antigen. However, a phenomenon of this type is not responsible for the failure of BALB/c mice reject B16 melanoma, since studies with H-2 recombinant mice have shown that B16 cells can be lysed by cytotoxic cells directed against either H-2K'' or H-2D'' antigens, although both of these antigens were expressed at low levels by B16 cells (31). Festenstein and coworkers (32; 33) have studied MHC Class 1 antigen expression in Gross virus-associated AKR leukaemias and leukaemic cell lines.…”

Section: Why Are Some Tumours Poorly Immunogenic?mentioning

confidence: 99%

The immunogenicity of tumour cells

Ashman

1987

Immunol Cell Biol

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Summary Immunological mechanisms are demonstrably of central importance in preventing the development of certain virus‐associated cancers in animals and man; however, they do not appear to fulfil this role in the majority of ‘spontaneous’ tumours. This does not, however, necessarily indicate that spontaneous tumours lack potential target antigens for immunologically mediated destruction. Work in the field of transplantation immunology has clearly shown that certain cell types fail to elicit rejection reactions despite their possession of alloantigens. Similarly, some tumour cell types are poorly immunogenic to the point that they can grow in and kill animals despite a major histocompatability barrier. These tumours are, however, susceptible to destruction in vivo in appropriately allo‐sensitized animals. Thus, some tumours may be able to grow in autologous or syngeneic hosts because of their poor immunogenicity, despite the fact that they express potential (tumour‐associated) rejection antigens. It may be possible to manipulate this situation for therapeutic purposes.

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“…26]. While the B16 melanoma is of low immunogenicity [27], the macrophages could be induced/activated by other tumor-related stimuli.…”

Section: Discussionmentioning

confidence: 99%

Differences between Beige and bg/+ Mice in the Disruption of Plasma Proteinase Regulation in the Tumor-Bearing State or following <i>Corynebacterium parvum</i> Treatment

Hart

1988

Pathophysiol Haemos Thromb

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Mice bearing the B16 melanoma or treated with Corynebacterium parvum develop elevated levels of plasma neutral proteinase activity. Similar experiments carried out with C57BL/6-bg/bg (beige) mice, which are genetically deficient in polymorphonuclear neutrophil (PMN) proteinases, revealed that such mice develop significantly diminished elevation in plasma proteinase activity compared to C57BL/6-bg/+ mice. Lysates of C. parvum elicited PMN from beige mice contained approximately 80% less neutral proteinase activity as did lysates of PMN from bg/+ mice. These results indicate that host cells, such as PMN, may become activated during the tumor progression, or following C.parvum treatment, causing degranulation and a subsequent elevation in plasma proteinase levels. If such an interpretation is correct, then this phenomenon may be the murine corollary to what has been observed in patients with certain inflammatory diseases or tumors.

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In vivo H‐2K and H‐2D antigen expression In two allogeneic mouse tumours of low immunogenicity

Cited by 8 publications

References 17 publications

Improved Anti-Tumour Adaptive Immunity Can Overcome the Melanoma Immunosuppressive Tumour Microenvironment

Improved Anti-Tumour Adaptive Immunity Can Overcome the Melanoma Immunosuppressive Tumour Microenvironment

The immunogenicity of tumour cells

Differences between Beige and bg/+ Mice in the Disruption of Plasma Proteinase Regulation in the Tumor-Bearing State or following <i>Corynebacterium parvum</i> Treatment

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