Tumor immunotherapy by converting tumor cells to MHC class II?positive, Ii protein?negative phenotype

Three new lymphoid tumors offering an assortment of variants in terms of MHC class I expressions, MHC class II expression, and Ig gene transcription have been discovered in the amphibianXenopus. One was developed in an individual of the isogenic LG15 clone (LG15/0), one in a frog of the LG15/40 clone (derived from a small egg recombinant of LG15), and one (ff-2) in a maleffsib of the individual in which MAR1, the first lymphoid tumor in Xenopus was found 2 years ago. These tumors developed primarily as thymus outgrowths and were transplantable in histocompatible tadpoles but not in nonhistocompatible hosts. Whereas LG15/0 and LG15/40 tumor cells also grow in adult LG15 frogs, theff-2 tumor, like the MAR1 cell line, is rejected by adultffanimals. Using flow cytometry with fluorescence-labeled antibodies and immunoprecipitation analysis, we could demonstrate that, like MAR1, these three new tumors express on their cell surface lymphopoietic markers recognized by mAbs FIF6 and RC47, as well as T-cell lineage markers recognized by mAbs AM22 (CD8-1ike) and X21.2, but not by immunologobulin (Ig) nor MHC class II molecules. Another lymphocyte-specific marker AM15 is expressed by 15/0 and 15/40 but notff-2 tumor cells. Theff-2 tumor cell expresses MHC class molecule in association withβ2-microglobulin on the surface, 15/40 cells contain cytoplasmic Iαchain that is barely detected at the cell surface by fluocytometry, and 15/0 cells do not synthesize class Iαchain at all. The three new tumors all produce large amounts of IgM mRNA of two different sizes but no Ig protein on the membrane nor in the cytoplasm. All tumor cell types synthesize large amount of Myc mRNA and MHC class I-like transcripts considered to be non classical.

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CIITA-Driven MHC Class II Expressing Tumor Cells as Antigen Presenting Cell Performers: Toward the Construction of an Optimal Anti-tumor Vaccine

Frontiers in Immunology ◽

10.3389/fimmu.2019.01806 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 8

Author(s):

Roberto S. Accolla ◽

Elise Ramia ◽

Alessandra Tedeschi ◽

Greta Forlani

Keyword(s):

Tumor Cells ◽

Mhc Class Ii ◽

Tumor Vaccine ◽

Class Ii ◽

Antigen Presenting Cell ◽

Antigen Presenting

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Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice.

Journal of Experimental Medicine ◽

10.1084/jem.181.2.619 ◽

1995 ◽

Vol 181 (2) ◽

pp. 619-629 ◽

Cited By ~ 135

Author(s):

S Baskar ◽

L Glimcher ◽

N Nabavi ◽

R T Jones ◽

S Ostrand-Rosenberg

Keyword(s):

Major Histocompatibility Complex ◽

Tumor Cells ◽

Mhc Class Ii ◽

Class Ii ◽

Genetically Engineered ◽

Tumor Rejection ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Cell Immunity ◽

Sarcoma Cells

Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7-transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.

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Deficient Major Histocompatibility Complex Class II Antigen Presentation in a Subset of Hodgkin's Disease Tumor Cells

Blood ◽

10.1182/blood.v92.7.2252 ◽

1998 ◽

Vol 92 (7) ◽

pp. 2252-2259 ◽

Cited By ~ 25

Author(s):

Herbert Bosshart ◽

Ruth F. Jarrett

Keyword(s):

Major Histocompatibility Complex ◽

Antigen Presentation ◽

Tumor Cells ◽

Mhc Class Ii ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Class Ii ◽

Histocompatibility Complex ◽

Class Ii Antigen ◽

Mhc Class Ii Molecules

Abstract Hodgkin's disease is a common malignancy of the lymphoid system. Although the scarce Hodgkin and Reed-Sternberg (HRS) tumor cells in involved tissue synthesize major histocompatibility complex (MHC) class II and costimulatory molecules such as CD40 or CD86, it is unclear whether these tumor cells are operational antigen-presenting cells (APC). We developed an immunofluorescence-based assay to determine the number of MHC class II molecules present on the surface of single living HRS cells. We found that in fresh Hodgkin's disease lymph node biopsies, a subset of HRS cells express a substantial number of surface MHC class II molecules that are occupied by MHC class II–associated invariant chain peptides (CLIP), indicating deficient loading of MHC class II molecules with antigenic peptides. Cultured Hodgkin's disease–derived (HD) cell lines, however, were found to express few MHC class II molecules carrying CLIP peptides on the cell surface and were shown to generate sodium dodecyl sulphate (SDS)-stable MHC class II αβ dimers. In addition to showing deficient MHC class II antigen presentation in a subset of HRS cells, our results show that the widely used HD-cell lines are not ideal in vitro models for the disease. The disruption of MHC class II–restricted antigen presentation in HRS cells could represent a key mechanism by which these tumor cells escape immune surveillance.

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