リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Aging-associated and CD4 T-cell–dependent ectopic CXCL13 activation predisposes to anti–PD-1 therapy-induced adverse events」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。
リケラボ

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Aging-associated and CD4 T-cell–dependent ectopic CXCL13 activation predisposes to anti–PD-1 therapy-induced adverse events

Tsukamoto, Hirotake Komohara, Yoshihiro Tomita, Yusuke Miura, Yuji Motoshima, Takanobu Imamura, Kosuke Kimura, Toshiki Ikeda, Tokunori Fujiwara, Yukio Yano, Hiromu Kamba, Tomomi Sakagami, Takuro Oshiumi, Hiroyuki 京都大学 DOI:10.1073/pnas.2205378119

2022.07.19

概要

Clinical success of immune-checkpoint blockade (ICB) cancer immunotherapy is compromised by increased risk of immune-related adverse events (irAEs). However, mechanistic action(s) of immune responses underlying development of irAE remain not fully explored. Here, we found that in tumor-bearing aged, but not young, mice, antiprogrammed death receptor (PD)-1 therapy elicited irAE-like multiorgan dysfunctions with ectopic accumulation of T and B cells in damaged organs. In this preclinical model, the organ toxicities were mediated by immunoglobulin G (IgG) deposition because administration of IG from ICB-treated aged mice induced the pathogenicity specifically in naïve aged hosts. Mechanistically, CD4 T-cell–derived interleukin (IL)-21 upregulated B-cell–homing chemokine, CXCL13, preferentially in irAE organs from aged mice treated with anti–PD-1 therapy. The ICB-induced pathogenicity was alleviated by B-cell depletion or by blockade of IL-21 or CXCL13 activity. These results suggest that age-associated immune regulatory milieu contributes to the formation of tertiary lymphoid structure-like lymphocytic aggregates in irAE organs and irAE-related toxicity employing IL-21-CXCL13-auto-antibody axis. Supporting this, a systemic increase in CXCL13 and Il21 expression in CD4 T cells correlated with irAE incidence in ICB-treated patients. These findings provide rationale for therapeutic usefulness of CXCL13 in irAE management.

論文の公開元へ

この論文で使われている画像

関連論文

関連論文をもっと見る

参考文献

1. M. Reck et al.; KEYNOTE-024 Investigators, Pembrolizumab versus chemotherapy for PD-L1- positive non-small-cell lung cancer. N. Engl. J. Med. 375, 1823–1833 (2016).

2. J. Larkin et al., Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23–34 (2015).

3. J. D. Wolchok et al., Overall survival with combined Nivolumab and Ipilimumab in advanced melanoma. N. Engl. J. Med. 377, 1345–1356 (2017).

4. T. Okazaki et al., Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med. 9, 1477–1483 (2003).

5. W. Hu, G. Wang, Y. Wang, M. J. Riese, M. You, Uncoupling therapeutic efficacy from immune- related adverse events in immune checkpoint blockade. iScience 23, 101580 (2020).

6. E. De Martin, J. M. Michot, O. Rosmorduc, C. Guettier, D. Samuel, Liver toxicity as a limiting factor to the increasing use of immune checkpoint inhibitors. JHEP Rep 2, 100170 (2020).

7. F. C. Santini et al., Safety and efficacy of re-treating with immunotherapy after immune-related adverse events in patients with NSCLC. Cancer Immunol. Res. 6, 1093–1099 (2018).

8. K. Esfahani et al., Moving towards personalized treatments of immune-related adverse events. Nat. Rev. Clin. Oncol. 17, 504–515 (2020).

9. A. Tokunaga et al., Selective inhibition of low-affinity memory CD8+ T cells by corticosteroids. J. Exp. Med. 216, 2701–2713 (2019).

10. X. Bai et al., Early use of high-dose glucocorticoid for the management of irAE is associated with poorer survival in patients with advanced melanoma treated with anti-PD-1 monotherapy. Clin. Cancer Res. 27, 5993–6000 (2021).

11. F. Berner et al., Association of checkpoint inhibitor-induced toxic effects with shared cancer and tissue antigens in non-small cell lung cancer. JAMA Oncol. 5, 1043–1047 (2019).

12. S. A. Tahir et al., Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities. Proc. Natl. Acad. Sci. U.S.A. 116, 22246–22251 (2019).

13. R. Das et al., Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J. Clin. Invest. 128, 715–720 (2018).

14. C. Calabrese et al., Polymyalgia rheumatica-like syndrome from checkpoint inhibitor therapy: Case series and systematic review of the literature. RMD Open 5, e000906 (2019).

15. E. P. Hoefsmit, E. A. Rozeman, J. B. A. G. Haanen, C. U. Blank, Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events. ESMO Open 4, e000472 (2019).

16. C. S. Pai et al., Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy- related toxicity. J. Clin. Invest. 129, 349–363 (2019).

17. B. D. Smith, G. L. Smith, A. Hurria, G. N. Hortobagyi, T. A. Buchholz, Future of cancer incidence in the United States: Burdens upon an aging, changing nation. J. Clin. Oncol. 27, 2758–2765 (2009).

18. C. Parry, E. E. Kent, A. B. Mariotto, C. M. Alfano, J. H. Rowland, Cancer survivors: A booming population. Cancer Epidemiol. Biomarkers Prev. 20, 1996–2005 (2011).

19. A. S. Betof et al., Impact of age on outcomes with immunotherapy for patients with melanoma. Oncologist 22, 963–971 (2017).

20. H. Matsuoka et al., Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody. BMC Cancer 20, 656 (2020).

21. X. Huang et al., Age-associated changes in adverse events arising from anti-PD-(L)1 therapy. Front. Oncol. 11, 619385 (2021).

22. H. Tsukamoto et al., Combined blockade of IL6 and PD-1/PD-L1 signaling abrogates mutual regulation of their immunosuppressive effects in the tumor microenvironment. Cancer Res. 78, 5011–5022 (2018).

23. J. Manola, M. Atkins, J. Ibrahim, J. Kirkwood, Prognostic factors in metastatic melanoma: A pooled analysis of Eastern Cooperative Oncology Group trials. J. Clin. Oncol. 18, 3782–3793 (2000).

24. H. Tsukamoto, S. Senju, K. Matsumura, S. L. Swain, Y. Nishimura, IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age. Nat. Commun. 6, 6702 (2015).

25. Y. Nakajima, K. Chamoto, T. Oura, T. Honjo, Critical role of the CD44lowCD62Llow CD8+ T cell subset in restoring antitumor immunity in aged mice. Proc. Natl. Acad. Sci. U.S.A. 118, e2103730118 (2021).

26. C. Winkler et al., Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD. Respir. Res. 12, 29 (2011).

27. F. Moazed et al., Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. Thorax 71, 1130–1136 (2016).

28. J. Rangel-Moreno, J. E. Moyron-Quiroz, L. Hartson, K. Kusser, T. D. Randall, Pulmonary expression of CXC chemokine ligand 13, CC chemokine ligand 19, and CC chemokine ligand 21 is essential for local immunity to influenza. Proc. Natl. Acad. Sci. U.S.A. 104, 10577–10582 (2007).

29. A. Nerviani, C. Pitzalis, Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer. J. Leukoc. Biol. 104, 333–341 (2018).

30. E. H. Choy et al., Translating IL-6 biology into effective treatments. Nat. Rev. Rheumatol. 16, 335–345 (2020).

31. T. T. Hansel, H. Kropshofer, T. Singer, J. A. Mitchell, A. J. George, The safety and side effects of monoclonal antibodies. Nat. Rev. Drug Discov. 9, 325–338 (2010).

32. J. J. Pillow, T. R. Korfhagen, M. Ikegami, P. D. Sly, Overexpression of TGF-alpha increases lung tissue hysteresivity in transgenic mice. J. Appl. Physiol. 91, 2730–2734 (2001).

33. H. Dai et al., Mechanical ventilation modulates Toll-like receptors 2, 4, and 9 on alveolar macrophages in a ventilator-induced lung injury model. J. Thorac. Dis. 7, 616–624 (2015).

34. K. Hatzi et al., BCL6 orchestrates Tfh cell differentiation via multiple distinct mechanisms. J. Exp. Med. 212, 539–553 (2015).

35. K. M. Ansel et al., A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 406, 309–314 (2000).

36. R. Cabrita et al., Tertiary lymphoid structures improve immunotherapy and survival in melanoma. Nature 577, 561–565 (2020).

37. M. Sznol et al., Pooled analysis safety profile of Nivolumab and Ipilimumab combination therapy in patients with advanced melanoma. J. Clin. Oncol. 35, 3815–3822 (2017).

38. V. Hurez et al., Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice. Cancer Res. 72, 2089–2099 (2012).

39. D. K. Finch, R. Ettinger, J. L. Karnell, R. Herbst, M. A. Sleeman, Effects of CXCL13 inhibition on lymphoid follicles in models of autoimmune disease. Eur. J. Clin. Invest. 43, 501–509 (2013).

40. Y. Wang et al., Cytoplasmic DNA sensing by KU complex in aged CD4+ T cell potentiates T cell activation and aging-related autoimmune inflammation. Immunity 54, 632–647.e9 (2021).

41. J. Merkenschlager et al., Dynamic regulation of TFH selection during the germinal centre reaction. Nature 591, 458–463 (2021).

42. M. A. Linterman et al., IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J. Exp. Med. 207, 353–363 (2010).

43. S. Goswami et al., ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC. Sci. Transl. Med. 12, eabc4220 (2020).

44. Q. Qi et al., Diversity and clonal selection in the human T-cell repertoire. Proc. Natl. Acad. Sci. U.S.A. 111, 13139–13144 (2014).

45. M. Ammirante, S. Shalapour, Y. Kang, C. A. Jamieson, M. Karin, Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts. Proc. Natl. Acad. Sci. U.S.A. 111, 14776–14781 (2014).

46. A. B. Rodriguez et al., Immune mechanisms orchestrate tertiary lymphoid structures in tumors via cancer-associated fibroblasts. Cell Rep. 36, 109422 (2021).

47. L. D. Falo, Jr, M. Kovacsovics-Bankowski, K. Thompson, K. L. Rock, Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity. Nat. Med. 1, 649–653 (1995).

48. H. Tsukamoto, Transcriptome analysis of whole lung tissue from anti-PD-1 therapy-treated mice. Gene Expression Omnibus. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184000. Deposited 30 May 2022.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文
を
一発検索！

この論文の関連論文を見る