Abstract
Immunotherapy is a quickly developing type of treatment and the future of therapy in oncology. This paper is a review of recent findings in the field of immunotherapy with an emphasis on immune checkpoint inhibitors. The challenges that immunotherapy might face in near future, such as primary and acquired resistance and the irAEs, are described in this article, as well as the perspectives such as identification of environmental modifiers of immunity and development of anti-cancer vaccines and combined therapies. There are multiple factors that may be responsible for immunoresistance, such as genomic factors, factors related to the immune system cells or to the cancer microenvironment, factors emerging from the host cells, as well as other factors such as advanced age, biological sex, diet, many hormones, existing comorbidities, and the gut microbiome.
Highlights
Despite several spectacular and successful immunotherapy trials of recent years, many cancer patients do not respond to immunotherapy, or their response remains shortlived, and the recurrence of the disease seems to be inevitable mainly due to the rapidly evolving resistance
Further research conducted on mice models showed clearly that MAPK inhibitors may restore the proper functioning of tumour infiltrating lymphocytes (TILs), as well as normal interferon γ related pathways and even MHC class I expression, which is often impaired in cancer cells [32–34]
In the case of melanoma, those patients possessing TME subtypes F and D experienced the worst outcomes to the immune checkpoint inhibitors, whereas IE TME carriers have generally favourable prognosis and may benefit the most from the immunotherapy [52]
Summary
Despite several spectacular and successful immunotherapy trials of recent years, many cancer patients do not respond to immunotherapy, or their response remains shortlived, and the recurrence of the disease seems to be inevitable mainly due to the rapidly evolving resistance. Further research conducted on mice models showed clearly that MAPK inhibitors may restore the proper functioning of TILs, as well as normal interferon γ related pathways and even MHC class I expression, which is often impaired in cancer cells [32–34] Another important factor, appearing to play a part in the immunotherapy resistance, is proteosomal degradation. High expression of CD73 is related with poor prognosis, for example in the case of pancreatic tumour, as well as some breast cancer subtypes It is connected with the resistance to the checkpoint inhibitors, especially anti-PD-1 mAbs, suggesting that CD73 might be considered as a potential biomarker [36,39]
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