24 research outputs found
The urgent need to recover MHC class I in cancers for effective immunotherapy
We would like to thank Dr M Bernal who has helped us in preparing the figure for the manuscript. This work was supported by grants co-financed by FEDER funds (EU) from the Instituto de Salud Carlos III (CP03/0111, PI12/02031, PI 08/1265, PI 11/01022, PI11/01386, PI14/01978, PI15/00528, RETIC RD 06/020, RD09/0076/00165, PT13/0010/0039), Junta de Andalucia in Spain (Group CTS-143, and CTS-695, CTS-3952, CVI-4740 and PI 09/0382 grant), Worldwide Cancer Research 15-1166 grant, and by Dutch Cancer Society (UL 2010-4785, TvH).Immune escape strategies aimed to avoid T-cell recognition, including the loss of tumor MHC class I expression, are commonly found in malignant cells. Tumor immune escape has proven to have a negative effect on the clinical outcome of cancer immunotherapy, including treatment with antibodies blocking immune checkpoint molecules. Hence, there is an urgent need to develop novel approaches to overcome tumor immune evasion. MHC class I antigen presentation is often affected in human cancers and the capacity to induce upregulation of MHC class I cell surface expression is a critical step in the induction of tumor rejection. This review focuses on characterization of rejection, escape, and dormant profiles of tumors and its microenvironment with a special emphasis on the tumor MHC class I expression. We also discuss possible approaches to recover MHC class I expression on tumor cells harboring reversible/‘soft’ or irreversible/‘hard’ genetic lesions. Such MHC class I recovery approaches might well synergize with complementary forms of immunotherapy.FEDER funds (EU) from the Instituto de Salud Carlos III
CP03/0111
PI12/02031
PI 08/1265
PI 11/01022
PI11/01386
PI14/01978
PI15/00528
RETIC RD 06/020
RD09/0076/00165
PT13/0010/0039Junta de Andalucía
CTS-143
CTS-695
CTS-3952
CVI-4740
PI 09/0382Worldwide Cancer Research
15-1166KWF Kankerbestrijding
UL 2010-478
Common Variable Immune Deficiency in Children—Clinical Characteristics Varies Depending on Defect in Peripheral B Cell Maturation
Gene regulation in Escherichia coli is commonly selected for both high plasticity and low noise
Bacteria often respond to dynamically changing environments by regulating gene expression. Despite this regulation being critically important for growth and survival, little is known about how selection shapes gene regulation in natural populations. To better understand the role natural selection plays in shaping bacterial gene regulation, here we compare differences in the regulatory behaviour of naturally segregating promoter variants from Escherichia coli (which have been subject to natural selection) to randomly mutated promoter variants (which have never been exposed to natural selection). We quantify gene expression phenotypes (expression level, plasticity and noise) for hundreds of promoter variants across multiple environments and show that segregating promoter variants are enriched for mutations with minimal effects on expression level. In many promoters, we infer that there is strong selection to maintain high levels of plasticity, and direct selection to decrease or increase cell-to-cell variability in expression. Taken together, these results expand our knowledge of how gene regulation is affected by natural selection and highlight the power of comparing naturally segregating polymorphisms to de novo random mutations to quantify the action of selection