Immunotherapy represents a hopeful approach to managing cancer patients, mostly due to its relatively high safety and durable effects. For more than a decade, immune checkpoint (IC) inhibitors have been amongst the most successful weapons in the anti-cancer arsenal, targeting key cellular and molecular processes within the tumor microenvironment (TME). However, even though IC-treatment is less toxic than other available anti-cancer therapies, emerged autoimmunity and immune-related adverse events (irAEs) are considered vulnerable points. Type-1 diabetes, myasthenia gravis, autoimmune encephalitis, myocarditis, autoimmune hypophysitis, arthritis, vasculitis, vitiligo, and psoriasis are included in disease conditions developed following treatment with anti-CTLA-4 and/or anti-PD-1/PD-L1 antibodies in patients with metastatic melanoma, small cell lung cancer, renal cancer, or metastatic prostate cancer. Additionally, individuals with pre-existing autoimmunity (rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, vasculitis, Sjögren’s syndrome) comprise a specific group of cancer patients who exhibit a high risk of autoimmune flare-up or irAEs upon IC-treatment.
The incidence of autoimmune and/or immune-related complications is probably undervalued due to many reasons including relatively short follow-ups, delayed onset of autoimmune/immune-related disorder, unclear etiology of symptoms, and cancer-associated death prior to the development of autoimmune disease. Furthermore, the landscape of cellular and molecular events underlying their pathogenetic mechanisms on the ground of cancer immunotherapy has not been fully elucidated. Their immunomodulatory function is mediated through diverse mechanisms inducing probably a series of immune-mediated events resulting in autoimmune manifestations, such as expansion of low-avidity T cells and depletion of regulatory T cells, cross-presentation of neoantigens, and epitope spreading. Moreover, epigenetic influence, transcription factor, and gene-enhancer expression may be involved in driving the plasticity of T cells. At the same time, the favorable clinical results of the first IC-inhibitors paved the way for the development of additional molecules that block novel ICs (antibodies against LAG-3, TIM-3, VISTA, TIGIT, PVRIG), which are now under large clinical trials assessing their potential in combinatorial treatment schemes (with other immune- or non-immune treatment schemes including vaccines, CAR T cells, oncolytic viruses, small-molecule inhibitors, chemotherapy and/or radiotherapy), aiming at the highest possible reactivation of anti-tumor immune responses. Thus, it is of utmost importance to be on guard for a rise in the incidence of immunotoxicity as these therapies become ever more widely used.
This Research Topic aims at gathering knowledge about the development or flare-up of autoimmune diseases and immune-related adverse effects in cancer patients upon mono- or combinatorial therapy including the use of antibodies against classical or novel ICs. Issues to be addressed regard but are not limited to the incidence of autoimmune or irAEs in IC-treated cancer patients, patient follow-up and monitoring upon IC-treatment, predictive and/or prognostic molecular biomarkers, cellular and molecular underlying pathogenetic mechanisms, specific concerns about patients with pre-existing autoimmunity. Rheumatologists, oncologists, immunologists, and molecular biologists are invited to contribute with Original Research Articles, Review and Systematic Review Articles, Brief Research Reports, Case Reports, or Clinical Trials Articles.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Immunotherapy represents a hopeful approach to managing cancer patients, mostly due to its relatively high safety and durable effects. For more than a decade, immune checkpoint (IC) inhibitors have been amongst the most successful weapons in the anti-cancer arsenal, targeting key cellular and molecular processes within the tumor microenvironment (TME). However, even though IC-treatment is less toxic than other available anti-cancer therapies, emerged autoimmunity and immune-related adverse events (irAEs) are considered vulnerable points. Type-1 diabetes, myasthenia gravis, autoimmune encephalitis, myocarditis, autoimmune hypophysitis, arthritis, vasculitis, vitiligo, and psoriasis are included in disease conditions developed following treatment with anti-CTLA-4 and/or anti-PD-1/PD-L1 antibodies in patients with metastatic melanoma, small cell lung cancer, renal cancer, or metastatic prostate cancer. Additionally, individuals with pre-existing autoimmunity (rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, vasculitis, Sjögren’s syndrome) comprise a specific group of cancer patients who exhibit a high risk of autoimmune flare-up or irAEs upon IC-treatment.
The incidence of autoimmune and/or immune-related complications is probably undervalued due to many reasons including relatively short follow-ups, delayed onset of autoimmune/immune-related disorder, unclear etiology of symptoms, and cancer-associated death prior to the development of autoimmune disease. Furthermore, the landscape of cellular and molecular events underlying their pathogenetic mechanisms on the ground of cancer immunotherapy has not been fully elucidated. Their immunomodulatory function is mediated through diverse mechanisms inducing probably a series of immune-mediated events resulting in autoimmune manifestations, such as expansion of low-avidity T cells and depletion of regulatory T cells, cross-presentation of neoantigens, and epitope spreading. Moreover, epigenetic influence, transcription factor, and gene-enhancer expression may be involved in driving the plasticity of T cells. At the same time, the favorable clinical results of the first IC-inhibitors paved the way for the development of additional molecules that block novel ICs (antibodies against LAG-3, TIM-3, VISTA, TIGIT, PVRIG), which are now under large clinical trials assessing their potential in combinatorial treatment schemes (with other immune- or non-immune treatment schemes including vaccines, CAR T cells, oncolytic viruses, small-molecule inhibitors, chemotherapy and/or radiotherapy), aiming at the highest possible reactivation of anti-tumor immune responses. Thus, it is of utmost importance to be on guard for a rise in the incidence of immunotoxicity as these therapies become ever more widely used.
This Research Topic aims at gathering knowledge about the development or flare-up of autoimmune diseases and immune-related adverse effects in cancer patients upon mono- or combinatorial therapy including the use of antibodies against classical or novel ICs. Issues to be addressed regard but are not limited to the incidence of autoimmune or irAEs in IC-treated cancer patients, patient follow-up and monitoring upon IC-treatment, predictive and/or prognostic molecular biomarkers, cellular and molecular underlying pathogenetic mechanisms, specific concerns about patients with pre-existing autoimmunity. Rheumatologists, oncologists, immunologists, and molecular biologists are invited to contribute with Original Research Articles, Review and Systematic Review Articles, Brief Research Reports, Case Reports, or Clinical Trials Articles.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.