New Research Revealed How Cancer Cells Develop Tolerance to Immunotherapy
Recently, scientists from the Fred Hutchinson Cancer Research Center used a new technique to observe the response of cancer cells under immunotherapy pressure. In a recent study published in Nature Communications, researchers used a newly developed technique to detect molecules in individual cells to provide an in-depth analysis of the response of patients with Merkel cell carcinoma to combination immunotherapy.
Because understanding the mechanisms of late/acquired immunotherapy tolerance is key to improving prognosis, clinical trials of cellular immunotherapy provide scientists with an excellent opportunity to understand complex tumor-immune cell interactions by characterizing t-cells-antigen interactions. To this end, the researchers treated two patients with merkel cell cancer using autologous CD8+T cells specific to merkel cell polyoma virus and immunocheckpoint inhibitors.
The researchers found that significant tumor regression in both patients was associated with infiltration of activated CD8+ T cells into regressed tumor tissue. But the two patients relapsed after 22 and 18 months, respectively. Subsequently, the researchers used single-cell DNA sequencing technology to analyze tumor tissue. They found that under intense CD8+T cell-mediated immune pressure, the transcription of specific HLA genes in targeted virus epitopes in tolerant tumor cells was dynamically suppressed, which was different from HLA gene deletion because the inhibition of the former was reversible.
Transcriptional repression of Class I loci may also be responsible for drug resistance in other immunotherapies (including immunological checkpoint treatment), a finding that will have a positive impact on the design of novel immunotherapeutics.