Autoimmune Responses in Oncology: Causes and Significance

Abstract

Specific anti-tumor immune responses have proven to be pivotal in shaping tumorigenesis and tumor progression in solid cancers. These responses can also be of an autoimmune nature, and autoantibodies can sometimes be present even before the onset of clinically overt disease. Autoantibodies can be generated due to mutated gene products, aberrant expression and post-transcriptional modification of proteins, a pro-immunogenic milieu, anti-cancer treatments, cross-reactivity of tumor-specific lymphocytes, epitope spreading, and microbiota-related and genetic factors. Understanding these responses has implications for both basic and clinical immunology. Autoantibodies in solid cancers can be used for early detection of cancer as well as for biomarkers of prognosis and treatment response. High-throughput techniques such as protein microarrays make parallel detection of multiple autoantibodies for increased specificity and sensitivity feasible, affordable, and quick. Cancer immunotherapy has revolutionized cancer treatments and has made a considerable impact on reducing cancer-associated morbidity and mortality. However, immunotherapeutic interventions such as immune checkpoint inhibition can induce immune-related toxicities, which can even be life-threatening. Uncovering the reasons for treatment-induced autoimmunity can lead to fine-tuning of cancer immunotherapy approaches to evade toxic events while inducing an effective anti-tumor immune response.

SARS-CoV-2 Infection Triggers Auto-Immune Response in ARDS

“…It has been suggested that some MHC molecules can present viral peptides with epitopes very similar to their own peptides, which may lead to the activation of autoreactive T cells. Variations in the MHC locus are also closely related to many different autoimmune diseases (7,45,46) given dysregulation, identification of AABs in COVID-19 and its associated pathologies, as we have observed in our results, have also been demonstrated in other studies about the diversity (47), frequency and suggested function of these AABs (48).…”

Effective Combination Immunotherapy with Oncolytic Adenovirus and Anti-PD-1 for Treatment of Human and Murine Ovarian Cancers

“…When the tumor is simultaneously treated by checkpoint inhibitors, the treatment might function as a boosting agent to upkeep this T cell reaction resulting in a synergistic outcome. As the goal of ICI is to activate the immune system to fight cancer, logically, the administration of ICI has been shown to cause some autoimmune reactions, manifesting usually as mild adverse events [ 36 ]. However, this phenomenon can be thought as potentially beneficial in our treatment setup.…”

Evaluation of the TCR Repertoire as a Predictive and Prognostic Biomarker in Cancer: Diversity or Clonality?

“…Finally, although the binding affinity of TCR to the self-peptides-MHC complexes has been reported to be much lower than to foreign antigens [ 60 ], the release of self-antigens in high concentrations may activate a high-dose/low-affinity response. This could compromise the peripheral tolerance, triggering autoimmune events [ 61 ].…”