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MHC Intratumoral Heterogeneity May Predict Cancer Progression and Response to Immunotherapy
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 9 (2018)
- Publication Year :
- 2018
- Publisher :
- Frontiers Media SA, 2018.
-
Abstract
- An individual tumor can present intratumoral phenotypic heterogeneity, containing tumor cells with different phenotypes that do not present irreversible genetic alterations. We have developed a mouse cancer model, named GR9, derived from a methylcholanthrene-induced fibrosarcoma that was adapted to tissue culture and cloned into different tumor cell lines. The clones showed diverse MHC-I phenotypes, ranging from highly positive to weakly positive MHC-I expression. These MHC-I alterations are due to reversible molecular mechanisms, because surface MHC-I could be recovered by IFN-γ treatment. Cell clones with high MHC-I expression demonstrated low local oncogenicity and high spontaneous metastatic capacity, whereas MHC-I-low clones showed high local oncogenicity and no spontaneous metastatic capacity. Although MHC-I-low clones did not metastasize, they produced MHC-I-positive dormant micrometastases controlled by the host immune system, i.e., in a state of immunodormancy. The metastatic capacity of each clone was directly correlated with the host T-cell subpopulations; thus, a strong decrease in cytotoxic and helper T lymphocytes was observed in mice with numerous metastases derived from MHC-I positive tumor clones but a strong increase was observed in those with dormant micrometastases. Immunotherapy was administered to the hosts after excision of the primary tumor, producing a recovery in their immune status and leading to the complete eradication of overt spontaneous metastases or their decrease. According to these findings, the combination of MHC-I surface expression in primary tumor and metastases with host T-cell subsets may be a decisive indicator of the clinical outcome and response to immunotherapy in metastatic disease, allowing the identification of responders to this approach.
- Subjects :
- lcsh:Immunologic diseases. Allergy
Male
0301 basic medicine
Helper T lymphocyte
Fibrosarcoma
medicine.medical_treatment
Immunology
T lymphocytes
Clone (cell biology)
chemical and pharmacologic phenomena
Docetaxel
Biology
Oncogenicity
03 medical and health sciences
0302 clinical medicine
Immune system
Polysaccharides
Cell Line, Tumor
medicine
Animals
Immunology and Allergy
Cytotoxic T cell
metastases
Original Research
Mice, Inbred BALB C
Histocompatibility Antigens Class I
Cancer
Immunotherapy
medicine.disease
Primary tumor
Disease Models, Animal
030104 developmental biology
Oligodeoxyribonucleotides
030220 oncology & carcinogenesis
intratumoral heterogeneity
Cancer research
immunotherapy
MHC
lcsh:RC581-607
Methylcholanthrene
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....6b298f4d727b7ee701bce1fe07b95a3d
- Full Text :
- https://doi.org/10.3389/fimmu.2018.00102