559
Views
5
CrossRef citations to date
0
Altmetric
Perspective

Immune checkpoint inhibitors for the treatment of sepsis:insights from preclinical and clinical development

, , & ORCID Icon
Pages 885-894 | Received 08 Apr 2022, Accepted 13 Jul 2022, Published online: 18 Aug 2022

References

  • Reinhart K, Daniels R, Kissoon N, et al. Recognizing sepsis as a global health priority - A WHO resolution. N Engl J Med. 2017;377(5):414–417.
  • Dupuis C, Bouadma L, Ruckly S, et al. Sepsis and septic shock in France: incidences, outcomes and costs of care. Ann Intensive Care. 2020;10(1):145.
  • Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study. Lancet. 2020;395(10219):200–211.
  • Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810.
  • Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121–137.
  • Torres LK, Pickkers P, van der Poll T. Sepsis-induced immunosuppression. Annu Rev Physiol. 2022;84:157–181.
  • MacGillivray DM, Kollmann TR. The role of environmental factors in modulating immune responses in early life. Front Immunol. 2014;5:434.
  • Childs CE, Calder PC, Miles EA. Diet and immune function. Nutrients. 2019;11(8):1933.
  • Shay K. Infectious complications of dental and periodontal diseases in the elderly population. Clin Infect Dis. 2002;34(9):1215–1223.
  • McLane LM, Abdel-Hakeem MS, Wherry EJ. CD8 T cell exhaustion during chronic viral infection and cancer. Annu Rev Immunol. 2019;37:457–495.
  • Wherry EJ. T cell exhaustion. Nat Immunol. 2011;12(6):492–499.
  • Pauken KE, Wherry EJ. Overcoming T cell exhaustion in infection and cancer. Trends Immunol. 2015;36(4):265–276.
  • Hirsch L, Zitvogel L, Eggermont A, et al. PD-Loma: a cancer entity with a shared sensitivity to the PD-1/PD-L1 pathway blockade. Br J Cancer. 2019;120(1):3–5.
  • Huang X, Venet F, Wang YL, et al. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A. 2009;106(15):6303–6308.
  • Young WA, Fallon EA, Heffernan DS, et al. Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates. Surgery. 2017;161(5):1387–1393.
  • Triantafyllou E, Gudd CL, Mawhin MA, et al. PD-1 blockade improves Kupffer cell bacterial clearance in acute liver injury. J Clin Invest. 2021;131(4):e140196.
  • Zhang Y, Zhou Y, Lou J, et al. PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Crit Care. 2010;14(6):R220.
  • Brahmamdam P, Inoue S, Unsinger J, et al. Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis. J Leukoc Biol. 2010;88(2):233–240.
  • Chen J, Chen R, Huang S, et al. Atezolizumab alleviates the immunosuppression induced by PDL1positive neutrophils and improves the survival of mice during sepsis. Mol Med Rep. 2021;23(2):1.
  • Curran CS, Busch LM, Li Y, et al. Anti-PD-L1 therapy does not improve survival in a murine model of lethal staphylococcus aureus Pneumonia. J Infect Dis. 2021;224(12):2073–2084.
  • Inoue S, Bo L, Bian J, et al. Dose-dependent effect of anti-CTLA-4 on survival in sepsis. Shock. 2011;36(1):38–44.
  • Chang KC, Burnham CA, Compton SM, et al. Blockade of the negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis. Crit Care. 2013;17(3):R85.
  • Vu CTB, Thammahong A, Yagita H, et al. Blockade of PD-1 attenuated postsepsis aspergillosis via the activation of ifn-gamma and the dampening of IL-10. Shock. 2020;53(4):514–524.
  • Shindo Y, Unsinger J, Burnham CA, et al. Interleukin-7 and anti-programmed cell death 1 antibody have differing effects to reverse sepsis-induced immunosuppression. Shock. 2015;43(4):334–343.
  • Zhang H, Chen C, He J, et al. Anti-PD-1 antibody administration following hip fracture surgery reverses immune dysfunction and decreases susceptibility to infection. Mediators Inflamm. 2019;2019:8492090.
  • Ruggeri T, Jacqueline C, Ambrosi X, et al. Immunotherapy with antiprogrammed cell death 1 antibody improves outcome in a mouse model of spinal cord injury followed by staphylococcus aureus Pneumonia. Crit Care Med. 2019;47(1):e28–e35.
  • Chen CW, Xue M, Zhang W, et al. 2B4 but not PD-1 blockade improves mortality in septic animals with preexisting malignancy. JCI Insight. 2019;4(22):e127867.
  • Busch LM, Sun J, Cui X, et al. Checkpoint inhibitor therapy in preclinical sepsis models: a systematic review and meta-analysis. Intensive Care Med Exp. 2020;8(1, 7):1–9.
  • Cavaillon JM, Singer M, Skirecki T. Sepsis therapies: learning from 30 years of failure of translational research to propose new leads. EMBO Mol Med. 2020;12(4):e10128.
  • Horiguchi H, Loftus TJ, Hawkins RB, et al. Innate immunity in the persistent inflammation, immunosuppression, and catabolism syndrome and its implications for therapy. Front Immunol. 2018;9:595.
  • Osuchowski MF, Ayala A, Bahrami S, et al. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis. Intensive Care Med Exp. 2018;6(1):26.
  • Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–874.
  • Hotchkiss RS, Moldawer LL. Parallels between cancer and infectious disease. N Engl J Med. 2014;371(4):380–383.
  • Cabrera-Perez J, Condotta SA, Badovinac VP, et al. Impact of sepsis on CD4 T cell immunity. J Leukoc Biol. 2014;96(5):767–777.
  • Odorizzi PM, Wherry EJ. Inhibitory receptors on lymphocytes: insights from infections. J Immunol. 2012;188(7):2957–2965.
  • Wakeley ME, Gray CC, Monaghan SF, et al. Check point inhibitors and their role in immunosuppression in sepsis. Crit Care Clin. 2020;36(1):69–88.
  • Shibru B, Fey K, Fricke S, et al. Detection of immune checkpoint receptors - a current challenge in clinical flow cytometry. Front Immunol. 2021;12:694055.
  • Shankar-Hari M, Datta D, Wilson J, et al. Early prediction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study. Intensive Care Med. 2018;44(11):1836–1848.
  • Bellesi S, Metafuni E, Hohaus S, et al. Increased CD95 (Fas) and PD-1 expression in peripheral blood T lymphocytes in COVID-19 patients. Br J Haematol. 2020;191(2):207–211.
  • Chen Z, John Wherry E. T cell responses in patients with COVID-19. Nat Rev Immunol. 2020;20(9):529–536.
  • Rha MS, Shin EC. Activation or exhaustion of CD8(+) T cells in patients with COVID-19. Cell Mol Immunol. 2021;18(10):2325–2333.
  • Remy KE, Mazer M, Striker DA, et al. Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections. JCI Insight. 2020;5(17):e140329.
  • Zheng M, Gao Y, Wang G, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol. 2020;17(5):533–535.
  • Bonifacius A, Tischer-Zimmermann S, Dragon AC, et al. COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Immunity. 2021;54(2):340–354 e346.
  • Loretelli C, Abdelsalam A, D’Addio F, et al. PD-1 blockade counteracts post-COVID-19 immune abnormalities and stimulates the anti-SARS-CoV-2 immune response. JCI Insight. 2021;6(24):e146701.
  • Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–168.
  • Johnson DB, Chandra S, Sosman JA. Immune checkpoint inhibitor toxicity in 2018. JAMA. 2018;320(16):1702–1703.
  • Hotchkiss RS, Colston E, Yende S, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med. 2019;45(10):1360–1371.
  • Watanabe E, Nishida O, Kakihana Y, et al. Pharmacokinetics, pharmacodynamics, and safety of nivolumab in patients with sepsis-induced immunosuppression: a multicenter, open-label phase 1/2 study. Shock. 2020;53(6):686–694.
  • Hotchkiss RS, Colston E, Yende S, et al. Immune checkpoint inhibition in sepsis: a phase 1b randomized, placebo-controlled, single ascending dose study of antiprogrammed cell death-ligand 1 antibody (BMS-936559). Crit Care Med. 2019;47(5):632–642.
  • Davenport EE, Burnham KL, Radhakrishnan J, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4(4):259–271.
  • Gardlund B, Dmitrieva NO, Pieper CF, et al. Six subphenotypes in septic shock: latent class analysis of the PROWESS shock study. J Crit Care. 2018;47:70–79.
  • Knox DB, Lanspa MJ, Kuttler KG, et al. Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome. Intensive Care Med. 2015;41(5):814–822.
  • Papin G, Bailly S, Dupuis C, et al. Clinical and biological clusters of sepsis patients using hierarchical clustering. Plos One. 2021;16(8):e0252793.
  • Scicluna BP, van Vught LA, Zwinderman AH, et al. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med. 2017;5(10):816–826.
  • Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003–2017.
  • Lu J, Chen R, Ou Y, et al. Characterization of immune-related genes and immune infiltration features for early diagnosis, prognosis and recognition of immunosuppression in sepsis. Int Immunopharmacol. 2022;107:108650.
  • Venet F, Textoris J, Blein S, et al. Immune profiling demonstrates a common immune signature of delayed acquired immunodeficiency in patients with various etiologies of severe injury. Crit Care Med. 2021;50(4):565–75.
  • Albert Vega C, Oriol G, Bartolo F, et al. Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study. Sci Rep. 2020;10(1):16136.
  • Tawfik DM, Vachot L, Bocquet A, et al. Immune profiling panel: a proof-of-concept study of a new multiplex molecular tool to assess the immune status of critically Ill patients. J Infect Dis. 2020;222(Suppl 2):S84–S95.
  • Peters-Sengers H, Butler JM, Uhel F, et al. Source-specific host response and outcomes in critically ill patients with sepsis: a prospective cohort study. Intensive Care Med. 2022;48(1):92–102.
  • Pereverzeva L, Uhel F, Peters Sengers H, et al. Association between delay in intensive care unit admission and the host response in patients with community-acquired pneumonia. Ann Intensive Care. 2021;11(1):142.
  • Yin J, Chen Y, Huang JL, et al. Prognosis-related classification and dynamic monitoring of immune status in patients with sepsis: a prospective observational study. World J Emerg Med. 2021;12(3):185–191.
  • Kronen R, Liang SY, Bochicchio G, et al. Invasive fungal infections secondary to traumatic injury. Int J Infect Dis. 2017;62:102–111.
  • Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. 2004;39(3):309–317.
  • Boddu P, Kantarjian H, Garcia-Manero G, et al. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma. 2018;59(4):790–802.
  • Spec A, Shindo Y, Burnham CA, et al. T cells from patients with Candida sepsis display a suppressive immunophenotype. Crit Care. 2016;20:15.
  • Grimaldi D, Pradier O, Hotchkiss RS, et al. Nivolumab plus interferon-gamma in the treatment of intractable mucormycosis. Lancet Infect Dis. 2017;17(1):18.
  • Banck JC, Mueller N, Mellinghoff SC, et al. Immune checkpoint blockade for aspergillosis and mucormycosis coinfection. Hemasphere. 2021;5(3):e530.
  • Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017;123(11):1904–1911.
  • Barnett R, Barta VS, Jhaveri KD. Preserved renal-allograft function and the PD-1 pathway inhibitor Nivolumab. N Engl J Med. 2017;376(2):191–192.
  • Cai H, Liu G, Zhong J, et al. Immune checkpoints in viral infections. Viruses. 2020; 12(9):1051.
  • Erickson JJ, Gilchuk P, Hastings AK, et al. Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest. 2012;122(8):2967–2982.
  • Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506.
  • Bidar F, Hamada S, Gossez M, et al. Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients. Ann Intensive Care. 2022;12(1):21.
  • Lombardi A, Villa S, Castelli V, et al. T-cell exhaustion in mycobacterium tuberculosis and nontuberculous mycobacteria infection: pathophysiology and therapeutic perspectives. Microorganisms. 2021;9(12):2460.
  • Barber DL, Mayer-Barber KD, Feng CG, et al. CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol. 2011;186(3):1598–1607.
  • Zaemes J, Kim C. Immune checkpoint inhibitor use and tuberculosis: a systematic review of the literature. Eur J Cancer. 2020;132:168–175.
  • Hagel S, Scherag A, Schuierer L, et al. Effect of antiviral therapy on the outcomes of mechanically ventilated patients with herpes simplex virus detected in the respiratory tract: a systematic review and meta-analysis. Crit Care. 2020;24(1):584.
  • Meyer A, Buetti N, Houhou-Fidouh N, et al. HSV-1 reactivation is associated with an increased risk of mortality and pneumonia in critically ill COVID-19 patients. Crit Care. 2021;25(1):417.
  • Srivastava R, Dervillez X, Khan AA, et al. The herpes simplex virus latency-associated transcript gene is associated with a broader repertoire of virus-specific exhausted CD8+ T cells retained within the trigeminal ganglia of latently infected hla transgenic rabbits. J Virol. 2016;90(8):3913–3928.
  • van Vught LA, Wiewel MA, Hoogendijk AJ, et al. The host response in patients with sepsis developing intensive care unit-acquired secondary infections. Am J Respir Crit Care Med. 2017;196(4):458–470.
  • Brands X, Haak BW, Klarenbeek AM, et al. Concurrent immune suppression and hyperinflammation in patients with community-acquired Pneumonia. Front Immunol. 2020;11:796.
  • Pickkers P. Simultaneously mounted pro- and anti-inflammatory host response relates to the development of secondary infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(4):406–407.
  • Cuenca AG, Maier RV, Cuschieri J, et al. The glue grant experience: characterizing the post injury genomic response. Eur J Trauma Emerg Surg. 2011;37(6):549–558.
  • Hotchkiss RS, Moldawer LL, Opal SM, et al. Sepsis and septic shock. Nat Rev Dis Primers. 2016;2:16045.
  • Cheng SC, Scicluna BP, Arts RJ, et al. Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis. Nat Immunol. 2016;17(4):406–413.
  • Wilson JK, Zhao Y, Singer M, et al. Lymphocyte subset expression and serum concentrations of PD-1/PD-L1 in sepsis - pilot study. Crit Care. 2018;22(1):95.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.