Indirect CD4<sup>+</sup> T‐cell‐mediated elimination of MHC II<sup>NEG</sup> tumor cells is spatially restricted and fails to prevent escape of antigen‐negative cells

Tveita, Anders Aune; Schjesvold, Fredrik; Sundnes, Olav; Haabeth, Ole Audun Werner; Haraldsen, Guttorm; Bogen, Bjarne

doi:10.1002/eji.201444659

Cited by 18 publications

(33 citation statements)

References 40 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Generation of mCherry- and GFP-expressing MOPC315, B16 and A20 cells was performed by lentiviral transduction, as previously described [22]. …”

Section: Methodsmentioning

confidence: 99%

“…Secreted antigen is taken up, processed and presented by tumor infiltrating macrophages [13]. Recognition by tumor infiltrating Th1 cells results in an IFN-γ-dependent induction of a cytotoxic M1 macrophage phenotype, resulting in tumor killing [13, 22]. However, it may be argued that despite the lack of constitutive MHC II expression, MOPC315 cells may start to express MHC class II under certain in vivo conditions, as observed for the B16 melanoma [1, 16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

et al. 2016

Self Cite

View full text Add to dashboard Cite

CD4+ T cells have been shown to reject tumor cells with no detectable expression of major histocompatibility complex class II (MHC II). However, under certain circumstances, induction of ectopic MHC II expression on tumor cells has been reported.To confirm that CD4+ T cell-mediated anti-tumor immunity can be successful in the complete absence of antigen display on the tumor cells themselves, we eliminated MHC II on tumor cells using CRISPR/Cas9. Our results demonstrate that ablation of the relevant MHC II (I-Ed) in multiple myeloma cells (MOPC315) does not hinder rejection by tumor-specific CD4+ T cells. These findings provide conclusive evidence that CD4+ T cells specific for tumor antigens can eliminate malignant cells in the absence of endogenous MHC class II expression on the tumor cells. This occurs through antigen uptake and indirect presentation on tumor-infiltrating macrophages.

show abstract

“…Generation of mCherry- and GFP-expressing MOPC315, B16 and A20 cells was performed by lentiviral transduction, as previously described [22]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indirect killing of MHC-II-negative tumour cells relies on tumour antigens taken up by MHC-II-positive macrophages that are processed and presented to CD4 + T cells in a bi-directional interaction leading to tumour cell killing by activated macrophages. In this context, the studies on the MOPC315 plasmacytoma tumour model produced relevant contributions 57–59…”

Section: Discussionmentioning

confidence: 99%

Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of myeloma

et al. 2015

View full text Add to dashboard Cite

In the Sp6 mouse plasmacytoma model, a whole-cell vaccination with Sp6 cells expressing de novo B7-1 (Sp6/B7) induced anatomically localized and cytotoxic T cell (CTL) -mediated protection against wild-type (WT) Sp6. Both WT Sp6 and Sp6/B7 showed down-regulated expression of MHC H-2 Ld. Increase of H-2 Ld expression by cDNA transfection (Sp6/B7/Ld) raised tumour immune protection and shifted most CTL responses towards H-2 Ld-restricted antigenic epitopes. The tumour-protective responses were not specific for the H-2 Ld-restricted immunodominant AH1 epitope of the gp70 common mouse tumour antigen, although WT Sp6 and transfectants were able to present it to specific T cells in vitro. Gp70 transcripts, absent in secondary lymphoid organs of naive mice, were detected in immunized mice as well as in splenocytes from naive mice incubated in vitro with supernatants of CTL-lysed Sp6 cell cultures, containing damage-associated molecular patterns (DAMPs). It has been shown that Toll-like receptor triggering induces gp70 expression. Damage-associated molecular patterns are released by CTL-mediated killing of Sp6/B7-Sp6/B7/Ld cells migrated to draining lymph nodes during immunization and may activate gp70 expression and presentation in most resident antigen-presenting cells. The same could also apply for Mus musculus endogenous ecotropic murine leukaemia virus 1 particles present in Sp6-cytosol, discharged by dying cells and superinfecting antigen-presenting cells. The outcome of such a massive gp70 cross-presentation would probably be tolerogenic for the high-affinity AH1-gp70-specific CTL clones. In this scenario, autologous whole-tumour-cell vaccines rescue tumour-specific immunoprotection by amplification of subdominant tumour antigen responses when those against the immune dominant antigens are lost.

show abstract

“…mCherry-labeled MOPC315 cells were generated as previously described (22). The Ig nonproducing variant MOPC315.36, and MOPC315.37, which retains FLCs intracellularly due to a point mutation (Ala 15 !Arg 15 ) in the L chain have been previously described (18).…”

Section: Cells and Reagentsmentioning

confidence: 99%

Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens

et al. 2015

Self Cite

View full text Add to dashboard Cite

Indirect CD4⁺ T‐cell‐mediated elimination of MHC II^NEG tumor cells is spatially restricted and fails to prevent escape of antigen‐negative cells

Cited by 18 publications

References 40 publications

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of myeloma

Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens

Contact Info

Product

Resources

About

Indirect CD4+ T‐cell‐mediated elimination of MHC IINEG tumor cells is spatially restricted and fails to prevent escape of antigen‐negative cells

Cited by 18 publications

References 40 publications

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

Tumor-specific CD4+ T cells eradicate myeloma cells genetically deficient in MHC class II display

Autologous cellular vaccine overcomes cancer immunoediting in a mouse model of myeloma

Tumors Escape CD4+ T-cell–Mediated Immunosurveillance by Impairing the Ability of Infiltrating Macrophages to Indirectly Present Tumor Antigens

Contact Info

Product

Resources

About

Indirect CD4⁺ T‐cell‐mediated elimination of MHC II^NEG tumor cells is spatially restricted and fails to prevent escape of antigen‐negative cells