Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors

Tocut, Milena; Brenner, Ronen; Zandman‐Goddard, Gisele

doi:10.1016/j.autrev.2018.01.010

Cited by 96 publications

(84 citation statements)

References 58 publications

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“…18 Furthermore, some patients develop ANA after immune checkpoint inhibitors such as PD-1 inhibitors, representing an enhanced immune activity against cancer. 19 In our study, we were not able to link any ANA-specific autoantibodies to the better survival noted in the ANApositive group. In the group negative for ANA by immunofluorescence we identified over 30 cases who had SSc-linked autoantibodies and when these were included in the ANA-positive group the link with ANA positivity and cancer survival remained strong.…”

Section: Discussioncontrasting

confidence: 74%

Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

et al. 2019

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Background: A higher rate of cancer in systemic sclerosis (SSc) is recognized but the role of SSc-linked autoantibodies status (positive/negative and autoantibody specificities) in the survival of SSc-patients with cancer remains poorly understood. Methods: We utilized the Clalit-Health-Services medical database in a case-control study to evaluate the autoantibody status and specificities of SSc-patients with age-and sex-matched controls with regard to the prevalence of different cancer-subtypes and their impact on mortality. SSc-linked autoantibodies (ANA, anti-centromere, anti-RNP, anti-RNA polymerase III (RNAPIII) and anti-Scl-70) status was assessed in terms of cancer risk and outcome. Results: 2,431 SSc-patients and 12,377 age-and sex-matched controls were included. SSc-patients had a relative risk of cancer of 1.90 (95%CI 1.62-2.24, p < 0.0001) and tended to develop malignancies earlier than controls. RNAPIII and Scl-70 autoantibody were associated with an increased overall cancer risk and after SSc diagnosis risk of cancer, respectively. As expected, SSc-patients with cancer had a risk of death of 2.15 (1.65-2.79) in comparison to SSc-patients without cancer. ANA-positive SSc-patients with cancer had a better prognosis than ANA-negative cases (p = 0.0001). Despite the benefit of ANA-positive status on survival, the anti-Scl-70-positive subgroup with cancer had a significant negative impact on the survival compared to Scl-70-positive cases without cancer, whereas anti-RNAPIII and anti-centromere had no significant impact. Conclusion: ANA positivity is an independent predictor of favorable prognosis in SSc-patients with cancer, possibly suggesting that humoral autoimmunity in SSc with cancer may have some benefit. However, no survival benefit was discernible with the common autoantibodies.

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Section: Discussioncontrasting

confidence: 74%

Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

et al. 2019

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“…Rheumatic disorders have been reported in this setting, mainly rheumatoid arthritis, polymyalgia rheumatica and systemic lupus erythematosus 1–3. Vasculitis seems to occur more seldom, with predominantly medium-vessel to large-vessel involvement 5. Here, we report on a patient with eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) following treatment with ICI for a stage IV melanoma.…”

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confidence: 93%

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors

et al. 2018

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“…The idea that the immune system in ALS/FTD patients is shifted toward a pro-inflammatory tone raises several interesting questions. It is becoming well established that cancer immunity and autoimmunity are two sides of the same coin, with checkpoint inhibitor therapy leading to both the promotion of tumor immunity as well as autoimmunity [ 148 ]. Antigen-presenting cells, such as dendritic cells, play a key role in driving the innate immune system tone and balancing tumor immunity vs. autoimmunity by the adaptive immune system [ 32 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Inflammation in ALS/FTD pathogenesis

McCauley¹,

2018

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Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that overlap in their clinical presentation, pathology and genetics, and likely represent a spectrum of one underlying disease. In ALS/FTD patients, neuroinflammation characterized by innate immune responses of tissue-resident glial cells is uniformly present on end-stage pathology, and human imaging studies and rodent models support that neuroinflammation begins early in disease pathogenesis. Additionally, changes in circulating immune cell populations and cytokines are found in ALS/FTD patients, and there is evidence for an autoinflammatory state. However, despite the prominent role of neuro- and systemic inflammation in ALS/FTD, and experimental evidence in rodents that altering microglial function can mitigate pathology, therapeutic approaches to decrease inflammation have thus far failed to alter disease course in humans. Here, we review the characteristics of inflammation in ALS/FTD in both the nervous and peripheral immune systems. We further discuss evidence for direct influence on immune cell function by mutations in ALS/FTD genes including C9orf72, TBK1 and OPTN, and how this could lead to the altered innate immune system “tone” observed in these patients.

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Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors

Cited by 96 publications

References 58 publications

Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

Autoantibody status in systemic sclerosis patients defines both cancer risk and survival with ANA negativity in cases with concomitant cancer having a worse survival

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) induced by immune checkpoint inhibitors

Inflammation in ALS/FTD pathogenesis

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