Inflammatory Thoracic Aortic Aneurysm in a Patient with Advanced Lung Adenocarcinoma Treated with Pembrolizumab

Ninomiya, Ryusuke; Kinehara, Yuhei; Tobita, Satoshi; Konaka, Hachiro; Jokoji, Ryu; Satō, Takashi; Tachibana, Isao

doi:10.2169/internalmedicine.8688-21

Cited by 7 publications

(3 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By using a previously established hypertensive model induced by Aldo-salt in aged mice ( 19 ), representing certain hypertensive populations, Mu and colleagues uncovered a mechanism by which androgens aggravate AA via the suppression of PD-1 expression in T cells within the spleen ( 18 ). This excellent study not only further emphasizes the potential of the Aldo-salt–induced AA model in the investigation of AA pathogenesis, but also provides clinical clues that immune checkpoint therapy in cancer treatment may adversely trigger the formation of AA in patients ( 25 ). Thus, imaging tests such as ultrasound for AA in patients with cancer undergoing such therapies may be promising in enhancing their health outcomes.…”

Section: Discussionmentioning

confidence: 70%

Unleashing PD-1: a duel of immunity in aortic aneurysm formation

Wang,

Chen,

Chang

2024

Journal of Clinical Investigation

View full text Add to dashboard Cite

Aortic aneurysms, particularly abdominal aortic aneurysms (AAAs), exhibit sex differences, with higher prevalence and severity in males than females, both in humans and experimental mouse models. In fact, male sex has been considered as the most potent nonmodifiable risk factor for AAA. Currently, there are no medications approved for the treatment of aortic aneurysms, despite the high lethality of ruptured aneurysms, which account for nearly 2% of all deaths. Moreover, the underlying molecular mechanisms mediating the sexual dimorphism of aortic aneurysms remain largely unknown. In this issue of the JCI , Mu et al. revealed a mechanism by which androgens, male sex hormones, exacerbate aortic aneurysms by suppressing programmed cell death protein 1 (PD-1) expression in T cells in an aldosterone and high salt–induced aortic aneurysm mouse model.

show abstract

Section: Discussionmentioning

confidence: 70%

Unleashing PD-1: a duel of immunity in aortic aneurysm formation

Wang,

Chen,

Chang

2024

Journal of Clinical Investigation

View full text Add to dashboard Cite

show abstract

“…In line with these clinical observations, the current study demonstrates for the first time that the treatment of mice with anti-PD-1 antibody can reinstate Aldo-salt-induced aortopathies (Figure 8), indicating an increased risk of developing aortic aneurysms for patients with immune checkpoint therapy. Consistent with this possibility, a recent case report shows that a 57-year-old man with lung adenocarcinoma treated with chemotherapy and immune checkpoint blockade developed inflammatory TAA (51). Hence, the current study suggests that cancer patients predisposed to the risk factors of aortic aneurysms (i.e., male, aging, and smoking) may have a chance to develop aortic aneurysms during immune checkpoint therapy and should be advised to screen for aortic aneurysms (i.e., subjected to ultrasound to screening aortic aneurysms) to increase life-saving power of cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 75%

Androgen aggravates aortic aneurysms via suppressing PD-1 in mice

Liu

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms, a devastating vascular disease with a higher prevalence and mortality rate in men than women. However, the molecular mechanism by which androgen mediates aortic aneurysms is largely unknown. Here, we report that male but not female mice develop aortic aneurysms in response to aldosterone and high salt (Aldo-salt). We demonstrate that both androgen and androgen receptors (AR) are crucial for the sexually dimorphic response to Aldo-salt. We identify T cells expressing programmed cell death protein 1 (PD-1), an immune checkpoint molecule important in immunity and cancer immunotherapy, as a key link between androgen and aortic aneurysms. We show that intraperitoneal injection of anti-PD-1 antibody reinstates Aldo-salt-induced aortic aneurysms in orchiectomized mice. Mechanistically, we demonstrate that AR binds to the PD-1 promoter to suppress its expression in the spleen. Hence, our study reveals an important but unexplored mechanism by which androgen contributes to aortic aneurysms by suppressing PD-1 expression in T cells. Our study also suggests that cancer patients predisposed to the risk factors of aortic aneurysms may be advised to screen for aortic aneurysms during immune checkpoint therapy.

show abstract

“…In alignment with these findings, the current studies suggest an increased risk of developing aortic aneurysms for patients undergoing immune checkpoint inhibitor therapy. Indeed, a recent case report shows that a 57-year-old man with lung adenocarcinoma treated with chemotherapy and immune checkpoint blockade developed inflammatory TAA (45). Thus, cancer patients predisposed to the risk factors of aortic aneurysms, such as being male, aging, and smoking, may have an increased likelihood of developing aortic aneurysms during immune checkpoint therapy.…”

Section: Discussionmentioning

confidence: 99%

Androgen aggravates aortic aneurysms via suppression of PD-1 in mice

Mu,

Liu,

Wang

et al. 2024

Journal of Clinical Investigation

View full text Add to dashboard Cite

Androgen has long been recognized for its pivotal role in the sexual dimorphism of cardiovascular diseases, including aortic aneurysms (AAs), a devastating vascular disease with a higher prevalence and fatality rate in men than in women. However, the mechanism by which androgen mediates AAs is largely unknown. Here, we found that male, not female, mice developed AAs when exposed to aldosterone and high salt (Aldo-salt). We revealed that androgen and androgen receptors (ARs) were crucial for this sexually dimorphic response to Aldo-salt. We identified programmed cell death protein 1 (PD-1), an immune checkpoint, as a key link between androgen and AAs. Furthermore, we demonstrated that administration of anti–PD-1 Ab and adoptive PD-1–deficient T cell transfer reinstated Aldo-salt–induced AAs in orchiectomized mice and that genetic deletion of PD-1 exacerbated AAs induced by a high-fat diet and angiotensin II (Ang II) in nonorchiectomized mice. Mechanistically, we discovered that the AR bound to the PD-1 promoter to suppress the expression of PD-1 in the spleen. Thus, our study unveils a mechanism by which androgen aggravates AAs by suppressing PD-1 expression in T cells. Moreover, our study suggests that some patients with cancer might benefit from screenings for AAs during immune checkpoint therapy.

show abstract

Inflammatory Thoracic Aortic Aneurysm in a Patient with Advanced Lung Adenocarcinoma Treated with Pembrolizumab

Cited by 7 publications

References 15 publications

Unleashing PD-1: a duel of immunity in aortic aneurysm formation

Unleashing PD-1: a duel of immunity in aortic aneurysm formation

Androgen aggravates aortic aneurysms via suppressing PD-1 in mice

Androgen aggravates aortic aneurysms via suppression of PD-1 in mice

Contact Info

Product

Resources

About