Immune profiles and clinical outcomes between sepsis patients with or without active cancer requiring admission to intensive care units

Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Kuo-Tung Huang, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin, Wen-Feng Fang, Yu-Mu Chen, Chiung-Yu Lin, Kuo-Tung Huang, Hsu-Ching Kao, Ying-Tang Fang, Chi-Han Huang, Ya-Ting Chang, Yi-His Wang, Chin-Chou Wang, Meng-Chih Lin

Abstract

Background: Immunoparalysis was observed in both patients with cancer and sepsis. In cancer patients, Cytotoxic T lymphocyte antigen-4 and programmed cell death protein 1/programmed death-ligand 1 axis are two key components of immunoparalysis. Several emerging therapies against these two axes gained significant clinical benefit. In severe sepsis patients, immunoparalysis was known as compensatory anti-inflammatory response syndrome and this has been suggested as an important cause of death in patients with sepsis. It would be interesting to see if immune status was different in severe sepsis patients with or without active cancer. The aim of this study was to assess the differences in immune profiles, and clinical outcomes between severe sepsis patients with or without cancer admitted to ICU.

Methods: A combined retrospective and prospective observational study from a cohort of adult sepsis patients admitted to three medical ICUs at Kaohsiung Chang Gung Memorial Hospital in Taiwan between August 2013 and June 2016.

Results: Of the 2744 patients admitted to the ICU, 532 patients with sepsis were included. Patients were divided into those with or without active cancer according to their medical history. Of the 532 patients, 95 (17.9%) patients had active cancer, and 437 (82.1%) patients had no active cancer history. Patients with active cancer were younger (p = 0.001) and were less likely to have diabetes mellitus (p < 0.001), hypertension (p < 0.001), coronary artery disease (p = 0.004), chronic obstructive pulmonary disease (p = 0.002) or stroke (p = 0.002) compared to patients without active cancer. Patients with active cancer also exhibited higher baseline lactate levels (p = 0.038), and higher baseline plasma interleukin (IL)-10 levels (p = 0.040), higher trend of granulocyte colony-stimulating factor (G-CSF) (p = 0.004) compared to patients without active cancer. The 14-day, 28-day and 90-day mortality rates were higher for patients with active cancer than those without active cancer (P < 0.001 for all intervals).

Conclusions: Among patients admitted to the ICU with sepsis, those with underling active cancer had higher baseline levels of plasma IL-10, higher trend of G-CSF and higher mortality rate than those without active cancer.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Patient inclusion and assignment.
Fig 1. Patient inclusion and assignment.
Fig 2. ICU mortality in patients with…
Fig 2. ICU mortality in patients with or without active malignancy.
Fig 3. ICU mortality in septic shock…
Fig 3. ICU mortality in septic shock patients with or without active malignancy (3A); ICU mortality in patients without shock with or without active malignancy (3B).
Fig 4. The ROC curve of IL-10…
Fig 4. The ROC curve of IL-10 for 28-day mortality prediction.
Fig 5. Influence of (A) baseline IL-10…
Fig 5. Influence of (A) baseline IL-10 and (B) trend of G-CSG and clinical outcome.

References

    1. Albano JD, Ward E, Jemal A, Anderson R, Cokkinides VE, Murray T, et al. Cancer mortality in the United States by education level and race. J Natl Cancer Inst. 2007;99(18):1384–94. doi: .
    1. Ferlay J, Parkin DM, Steliarova-Foucher E. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010;46(4):765–81. doi: .
    1. Lim GH, Chow KY, Lee HP. Singapore cancer trends in the last decade. Singapore Med J. 2012;53(1):3–9; quiz 10. .
    1. Bird GT, Farquhar-Smith P, Wigmore T, Potter M, Gruber PC. Outcomes and prognostic factors in patients with haematological malignancy admitted to a specialist cancer intensive care unit: a 5 yr study. Br J Anaesth. 2012;108(3):452–9. doi: .
    1. Hawari FI, Nazer LH, Addassi A, Rimawi D, Jamal K. Predictors of ICU Admission in Patients With Cancer and the Related Characteristics and Outcomes: A 5-Year Registry-Based Study. Crit Care Med. 2016;44(3):548–53. doi: .
    1. Allareddy V, Prakasam S, Allareddy V, Martinez-Schlurmann NI, Rampa S, Nalliah RP, et al. Poor Oral Health Linked with Increased Risk of Infectious Complications in Adults with Leukemia. J Mass Dent Soc. 2015;64(3):38–42. .
    1. Obeng-Nkrumah N, Labi AK, Acquah ME, Donkor ES. Bloodstream infections in patients with malignancies: implications for antibiotic treatment in a Ghanaian tertiary setting. BMC Res Notes. 2015;8:742 doi: ;.
    1. Soares M, Caruso P, Silva E, Teles JM, Lobo SM, Friedman G, et al. Characteristics and outcomes of patients with cancer requiring admission to intensive care units: a prospective multicenter study. Crit Care Med. 2010;38(1):9–15. doi: .
    1. Cohen J, Pivodic L, Miccinesi G, Onwuteaka-Philipsen BD, Naylor WA, Wilson DM, et al. International study of the place of death of people with cancer: a population-level comparison of 14 countries across 4 continents using death certificate data. Br J Cancer. 2015;113(9):1397–404. doi: ;.
    1. Gomes B, Higginson IJ, Calanzani N, Cohen J, Deliens L, Daveson BA, et al. Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain. Ann Oncol. 2012;23(8):2006–15. doi: .
    1. Jarosek SL, Shippee TP, Virnig BA. Place of Death of Individuals with Terminal Cancer: New Insights from Medicare Hospice Place-of-Service Codes. J Am Geriatr Soc. 2016. doi: .
    1. O'Dowd EL, McKeever TM, Baldwin DR, Hubbard RB. Place of Death in Patients with Lung Cancer: A Retrospective Cohort Study from 2004–2013. PLoS One. 2016;11(8):e0161399 doi: .
    1. Wright AA, Keating NL, Ayanian JZ, Chrischilles EA, Kahn KL, Ritchie CS, et al. Family Perspectives on Aggressive Cancer Care Near the End of Life. JAMA. 2016;315(3):284–92. doi: ;.
    1. Santegoets SJ, Welters MJ, van der Burg SH. Monitoring of the Immune Dysfunction in Cancer Patients. Vaccines (Basel). 2016;4(3). doi: ;.
    1. Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23 Suppl 8:viii6–9. doi: ;.
    1. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480(7378):480–9. doi: ;.
    1. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65. doi: ;.
    1. Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123–35. doi: ;.
    1. Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–33. doi: .
    1. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi: ;.
    1. Young KH, Baird JR, Savage T, Cottam B, Friedman D, Bambina S, et al. Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy. PLoS One. 2016;11(6):e0157164 doi: ;.
    1. Arens C, Bajwa SA, Koch C, Siegler BH, Schneck E, Hecker A, et al. Sepsis-induced long-term immune paralysis—results of a descriptive, explorative study. Crit Care. 2016;20:93 doi: ;.
    1. Sundar KM, Sires M. Sepsis induced immunosuppression: Implications for secondary infections and complications. Indian J Crit Care Med. 2013;17(3):162–9. doi: ;.
    1. Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13(12):862–74. Epub 2013/11/16. doi: ;.
    1. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31(4):1250–6. Epub 2003/04/12. doi: .
    1. Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):775–87. Epub 2016/02/24. doi: ;.
    1. Taccone FS, Artigas AA, Sprung CL, Moreno R, Sakr Y, Vincent JL. Characteristics and outcomes of cancer patients in European ICUs. Crit Care. 2009;13(1):R15 doi: ;.
    1. Landy R, Pesola F, Castanon A, Sasieni P. Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case-control study. Br J Cancer. 2016. doi: .
    1. Murphy CC, Sandler RS, Sanoff HK, Yang YC, Lund JL, Baron JA. Decrease in incidence of colorectal cancer among individuals 50 years or older following recommendations for population-based screening. Clin Gastroenterol Hepatol. 2016. doi: .
    1. Katki HA, Kovalchik SA, Berg CD, Cheung LC, Chaturvedi AK. Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening. JAMA. 2016;315(21):2300–11. doi: ;.
    1. Tammemagi MC, Katki HA, Hocking WG, Church TR, Caporaso N, Kvale PA, et al. Selection criteria for lung-cancer screening. N Engl J Med. 2013;368(8):728–36. doi: ;.
    1. Xiao LH, Chen PR, Gou ZP, Li YZ, Li M, Xiang LC, et al. Prostate cancer prediction using the random forest algorithm that takes into account transrectal ultrasound findings, age, and serum levels of prostate-specific antigen. Asian J Androl. 2016. doi: .
    1. Lee LC, Hu CC, Loh el W, Hwang SF. Factors affecting the place of death among hospice home care cancer patients in Taiwan. Am J Hosp Palliat Care. 2014;31(3):300–6. doi: .
    1. Monneret G, Venet F, Pachot A, Lepape A. Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony. Mol Med. 2008;14(1–2):64–78. doi: ;.
    1. Vanska M, Koivula I, Jantunen E, Hamalainen S, Purhonen AK, Pulkki K, et al. IL-10 combined with procalcitonin improves early prediction of complications of febrile neutropenia in hematological patients. Cytokine. 2012;60(3):787–92. doi: .
    1. Urbonas V, Eidukaite A, Tamuliene I. Increased interleukin-10 levels correlate with bacteremia and sepsis in febrile neutropenia pediatric oncology patients. Cytokine. 2012;57(3):313–5. doi: .
    1. Yende S, D'Angelo G, Kellum JA, Weissfeld L, Fine J, Welch RD, et al. Inflammatory markers at hospital discharge predict subsequent mortality after pneumonia and sepsis. Am J Respir Crit Care Med. 2008;177(11):1242–7. doi: ;.
    1. Schaper F, Rose-John S. Interleukin-6: Biology, signaling and strategies of blockade. Cytokine Growth Factor Rev. 2015;26(5):475–87. doi: .
    1. Pencik J, Schlederer M, Gruber W, Unger C, Walker SM, Chalaris A, et al. STAT3 regulated ARF expression suppresses prostate cancer metastasis. Nat Commun. 2015;6:7736 doi: ;.
    1. Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, et al. Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst. 2011;103(14):1112–22. doi: ;.
    1. Mhaskar R, Clark OA, Lyman G, Engel Ayer Botrel T, Morganti Paladini L, Djulbegovic B. Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev. 2014;(10):CD003039 doi: .
    1. Reilly JP, Anderson BJ, Hudock KM, Dunn TG, Kazi A, Tommasini A, et al. Neutropenic sepsis is associated with distinct clinical and biological characteristics: a cohort study of severe sepsis. Crit Care. 2016;20(1):222 doi: ;.
    1. Kumar S, Rizvi M. Serum tumor necrosis factor alpha and C-reactive protein in pediatric patients with sepsis and its correlation with microbiologic findings. Indian J Pathol Microbiol. 2010;53(3):494–7. .
    1. Casey LC, Balk RA, Bone RC. Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med. 1993;119(8):771–8. .
    1. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275–85. doi: .
    1. Monneret G, Venet F. Monocyte HLA-DR in sepsis: shall we stop following the flow? Crit Care. 2014;18(1):102 Epub 2014/01/08. doi: ;.
    1. van den Berk JM, Oldenburger RH, van den Berg AP, Klompmaker IJ, Mesander G, van Son WJ, et al. Low HLA-DR expression on monocytes as a prognostic marker for bacterial sepsis after liver transplantation. Transplantation. 1997;63(12):1846–8. .
    1. Samuels S, Spaans VM, Osse M, Peters LA, Kenter GG, Fleuren GJ, et al. Human Leukocyte Antigen-DR Expression is Significantly Related to an Increased Disease-Free and Disease-Specific Survival in Patients With Cervical Adenocarcinoma. Int J Gynecol Cancer. 2016;26(8):1503–9. doi: .
    1. Wittayachamnankul B, Chentanakij B, Sruamsiri K, Chattipakorn N. The role of central venous oxygen saturation, blood lactate, and central venous-to-arterial carbon dioxide partial pressure difference as a goal and prognosis of sepsis treatment. J Crit Care. 2016;36:223–9. doi: .

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