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

2019 ARIA Care pathways for allergen immunotherapy.

Abstract Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients