The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study

Özkara, Selvinaz; akyüz, cebrail; Gül, Mehmet Onur

doi:10.55730/1300-0144.5408

The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study

Mehmet Onur GÜL, (Çukurova Üniversitesi, Balcalı Eğitim ve Araştırma Hastanesi, Cerrahi Onkoloji Bölümü, Adana, Türkiye)

Cebrail AKYÜZ, (Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Gastroenterolojik Cerrahi Bölümü, İstanbul, Türkiye)

Selvinaz ÖZKARA (Haydarpaşa Numune Eğitim ve Araştırma Hastanesi, Patoloji Bölümü, İstanbul, Türkiye)

Turkish Journal of Medical Sciences

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Yıl: 2022 Cilt: 52 Sayı: 4 Sayfa Aralığı: 1058 - 1066 Metin Dili: İngilizce DOI: 10.55730/1300-0144.5408 İndeks Tarihi: 14-12-2022

The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study

Öz:

Background/aim: The rationale behind using immunonutrition in cancer patients is to prevent malnutrition, manage the host’s immune response, and keep cancer under control by utilizing the potential immune system available in the host against the tumor. This prospective- study aims to assess the impact of immunonutrition on tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. Materials and methods: This is a single-center, prospective study. Forty patients diagnosed with middle and lower rectal tumors were enrolled in the study between March 2018 and December 2019. Nutrition protocols were given to all study subjects prior to surgery. Tissue CD4, CD8, and Fox P3 expression prior to enrollment (endoscopic biopsy specimens) and following surgery (resected tissue) were compared. Results: Longitudinal data was available for 30 patients. In the present study, 15 patients were given immuno-nutrition, and 15 patients received standard nutrition. The immunonutrition and standard nutrition groups were similar regarding CD4 [10 (5–20) vs. 10 (10–10), p = 0.653], CD8 [30 (20–35) vs. 30 (20–40), p = 0.870], lymphocyte counts [2 (2–3) vs. 2 (2–3), p = 0.325], fox p3 value [10 (10–10) vs. 10 (10–10), p = 0.775], and CD4/CD8 ratio [0.33 (0.29–0.66) vs. 0.50 (0.29–0.50), p = 0.870] on endoscopic biopsy. CD4 [10 (7.5–25) vs. 30 (10–50), p = 0.050], CD8 [60 (40–60) vs. 50 (40–60), p = 0.713] and Fox P3 [10 (5–10) vs. 10 (2.5–10), p = 0.935] were also similar in tissues extracted by surgery. However, the standard nutrition group had significantly higher CD4/CD8 values in their tissues removed on surgery [0.25 (0.14–0.50) vs. 0.66 (0.28–1), p = 0.026] Conclusion: The present study revealed that CD4/CD8 ratios were lower in the immunonutrition group in comparison to the group receiving standard nutritional supplements before surgery.

Anahtar Kelime: Colorectal cancer nutrition regulatory t cells tumor infiltrative lymphocytes

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Bosset JF, Collette L, Calais G, Mineur L, Maingon P et al. Chemotherapy with preoperative radiotherapy in rectal cancer. New England Journal of Medicine 2006; 355 (11): 1114–1123. doi: 10.1056/NEJMoa060829
2. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ ARO/AIO-94 randomized phase III trial after a median follow- up of 11 years. Journal of Clinical Oncology 2012; 30 (16): 1926–1933. doi: 10.1016/s0022-5347(17)76858-9
3. Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta- analysis. Annals of Surgical Oncology 2012; 19 (9): 2822–2832. doi: 10.1245/s10434-011-2209-y
4. Waitzberg DL, Ravacci GR, Raslan M. Hospital hyponutrition. Nutrición Hospitalaria 2011; 26 (2): 254-264. doi: 10.1590/ S0212-16112011000200003
5. García A, Álvarez J, Planas MS, Burgos R, Araujo K. Multidisciplinary consensus on the approach to hospital malnutrition in Spain. Nutrición Hospitalaria 2011; 26 (4): 701-710. doi: 10.1590/s0212-16112011000400006
6. Cid L, Fernández T, Neira P, Arias J, Varela JJ et al. Hyponutrition prevalence among patients with digestive neo-plasm before surgery. Nutrición Hospitalaria 2008; 23 (1): 46-53.
7. Swann JB, Smyth MJ. Immune surveillance of tumors. The Journal of Clinical Investigation 2007; 117 (5): 1137–1146. doi: 10.1172/jci31405
8. Dieci MV, Criscitiello C, Goubar A, Viale G, Conte P et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Annals of Oncology 2014; 25 (7): 611–618. doi: 10.1093/annonc/mdt556
9. Demaria S, Formenti SC. Radiation as an immunological adjuvant: current evidence on dose and fractionation. Frontiers in Oncology 2012; 2: 153. doi: 10.3389/fonc.2012.00153
10. Chen XY, Yeong J, Thike AA, Bay BH, Tan PH. Prognostic role of immune infiltrates in breast ductal carcinoma in situ. Breast Cancer Research and Treatment 2019; 177 (1): 17–27. doi: 10.1007/s10549-019-05272-2
11. Salama P, Phillips M, Grieu F, Morris M, Zeps N et al. Tumor- infiltrating FOXP3 T regulatory cells show strong prognostic significance in colorectal cancer. Journal of Clinical Oncology 2009; 27 (2): 186–192. doi: 10.1200/jco.2008.18.7229
12. Correale P, Rotundo MS, Del Vecchio MT, Remondo C, Migali C et al. Regulatory (FoxP3) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy. Journal of Immunotherapy 2010; 33 (4): 435–441. doi: 10.1097/ CJI.0b013e3181d32f01
13. Luen S, Virassamy B, Savas P, Salgado R, Loi S. The genomic landscape of breast cancer and its interaction with host immunity. The Breast 2016; 29: 241–250. doi: 10.1016/j. breast.2016.07.015
14. Peker KD, Ozkanli SS, Akyuz C, Uzun O, Yasar NF et al. Preoperative immunonutrition regulates tumor infiltrative lymphocytes and increases tumor angiogenesis in gastric cancer patients. Archives of Medical Science 2017; 13 (6): 1365-1372. doi: 10.5114/aoms.2016.60054
15. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ et al. NCCN Guidelines Insights: Rectal Cancer, Version 6.2020. Journal of the National Comprehensive Cancer Network 2020; 18 (7): 806-815. doi: 10.6004/jnccn.2020.0032
16. Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Ad Hoc ESPEN Working Group. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clinical Nutrition 2003; 22 (3): 321-36. doi: 10.1016/ s0261-5614(02)00214-5
17. Cederholm T, Barazzoni R, Austin P, Ballmer P, Biolo G et al. ESPEN guidelines on definitions and terminology of clinical nutrition. Clinical Nutrition 2017; 36 (1): 49-64. doi: 10.1016/j. clnu.2016.09.004
18. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (5): 646–674. doi: 10.1016/j. cell.2011.02.013
19. Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes and Development 2018; 32 (19-20): 1267-1284. doi: 10.1101/gad.314617.118
20. Matsushita H, Vesely MD, Koboldt DC, Rickert CG, Uppaluri R et al. Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 2012; 482 (7385): 400-404. doi: 10.1038/nature10755
21. Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. The Journal of Pathology 2010; 222 (4): 350–366. doi: 10.1002/path.2774
22. Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N et al. Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clinical Cancer Research 2014; 20 (7): 1891–1899. doi: 10.1158/1078-0432.CCR-13-2830
23. Klintrup K, Mäkinen JM, Kauppila S, Väre PO, Melkko J et al. Inflammation and prognosis in colorectal cancer. European Journal of Cancer 2005; 41 (17): 2645-2654. doi: 10.1016/j. ejca.2005.07.017
24. Roxburgh CS, Salmond JM, Horgan PG, Oien KA, McMillan DC. Comparison of the prognostic value of inflammation- based pathologic and biochemical criteria in patients undergoing potentially curative resection for colorectal cancer. Annals of Surgery 2009; 249 (5): 788-793. doi: 10.1097/ SLA.0b013e3181a3e738
25. Huh JW, Lee JH, Kim HR. Prognostic significance of tumor- infiltrating lymphocytes for patients with colorectal cancer. Archives of Surgery 2012; 147 (4): 366-372. doi: 10.1001/ archsurg.2012.35
26. Shinto E, Hase K, Hashiguchi Y, Sekizawa A, Ueno H et al. CD8+ and FOXP3+ tumor-infiltrating T cells before and after chemoradiotherapy for rectal cancer. Annals of Surgical Oncology 2014; 21 (3): 414-421. doi: 10.1245/s10434-014- 3584-y
27. Morris M, Platell C, de Boer B, McCaul K, Iacopetta B. Population-based study of prognostic factors in stage II colonic cancer. The British Journal of Surgery 2006; 93 (7): 866-871. doi: 10.1002/bjs.5345
28. Caglayan K, Oner I, Gunerhan Y, Ata P, Koksal N et al. The impact of preoperative immunonutrition and other nutrition models on tumor infiltrative lymphocytes in colorectal cancer patients. American Journal of Surgery 2012; 204 (4): 416-421. doi: 10.1016/j.amjsurg.2011.12.018
29. Diederichsen AC, Hjelmborg Jv, Christensen PB, Zeuthen J, Fenger C. Prognostic value of the CD4+/CD8+ ratio of tumour infiltrating lymphocytes in colorectal cancer and HLA-DR expression on tumour cells. Cancer Immunology, Immunotherapy 2003; 52 (7): 423-428. doi: 10.1007/s00262- 003-0388-5
30. Fluxá P, Rojas-Sepúlveda D, Gleisner MA, Tittarelli A, Villegas P et al. High CD8+ and absence of Foxp3+ T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival. BMC Cancer 2018; 18 (1): 243. doi: 10.1186/ s12885-018-4147-6
31. Waki K, Kawano K, Tsuda N, Komatsu N, Yamada A. CD4/ CD8 ratio is a prognostic factor in IgG nonresponders among peptide vaccine-treated ovarian cancer patients. Cancer Science 2020; 111 (4): 1124-1131. doi: 10.1111/cas.14349
32. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology 2003; 4 (4): 330-336. doi: 10.1038/ ni904
33. Perrone G, Ruffini PA, Catalano V, Spino C, Santini D et al. Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. European Journal of Cancer 2008; 44 (13): 1875-1882. doi: 10.1016/j.ejca.2008.05.017
34. Ohtani H. Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human colorectal cancer. Cancer Immunity 2007; 7 (1): 4.
35. Chew A, Salama P, Robbshaw A, Klopcic B, Zeps N et al. SPARC, FOXP3, CD8 and CD45 correlation with disease recurrence and long-term disease-free survival in colorectal cancer. Public Library of Science One 2011; 6 (7): e22047. doi: 10.1371/journal.pone.0022047

APA	Gül M, akyüz c, Özkara S (2022). The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. , 1058 - 1066. 10.55730/1300-0144.5408
Chicago	Gül Mehmet Onur,akyüz cebrail,Özkara Selvinaz The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. (2022): 1058 - 1066. 10.55730/1300-0144.5408
MLA	Gül Mehmet Onur,akyüz cebrail,Özkara Selvinaz The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. , 2022, ss.1058 - 1066. 10.55730/1300-0144.5408
AMA	Gül M,akyüz c,Özkara S The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. . 2022; 1058 - 1066. 10.55730/1300-0144.5408
Vancouver	Gül M,akyüz c,Özkara S The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. . 2022; 1058 - 1066. 10.55730/1300-0144.5408
IEEE	Gül M,akyüz c,Özkara S "The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study." , ss.1058 - 1066, 2022. 10.55730/1300-0144.5408
ISNAD	Gül, Mehmet Onur vd. "The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study". (2022), 1058-1066. https://doi.org/10.55730/1300-0144.5408

APA	Gül M, akyüz c, Özkara S (2022). The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. Turkish Journal of Medical Sciences, 52(4), 1058 - 1066. 10.55730/1300-0144.5408
Chicago	Gül Mehmet Onur,akyüz cebrail,Özkara Selvinaz The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. Turkish Journal of Medical Sciences 52, no.4 (2022): 1058 - 1066. 10.55730/1300-0144.5408
MLA	Gül Mehmet Onur,akyüz cebrail,Özkara Selvinaz The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. Turkish Journal of Medical Sciences, vol.52, no.4, 2022, ss.1058 - 1066. 10.55730/1300-0144.5408
AMA	Gül M,akyüz c,Özkara S The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. Turkish Journal of Medical Sciences. 2022; 52(4): 1058 - 1066. 10.55730/1300-0144.5408
Vancouver	Gül M,akyüz c,Özkara S The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study. Turkish Journal of Medical Sciences. 2022; 52(4): 1058 - 1066. 10.55730/1300-0144.5408
IEEE	Gül M,akyüz c,Özkara S "The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study." Turkish Journal of Medical Sciences, 52, ss.1058 - 1066, 2022. 10.55730/1300-0144.5408
ISNAD	Gül, Mehmet Onur vd. "The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study". Turkish Journal of Medical Sciences 52/4 (2022), 1058-1066. https://doi.org/10.55730/1300-0144.5408