WordNet

an agranulocytic leukocyte that normally makes up a quarter of the white blood cell count but increases in the presence of infection (同)lymph cell
an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/17 03:37:39」(JST)

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Tumor infiltrating lymphocytes (TILs) are a type of white blood cell found in tumors. TILs are implicated in killing tumor cells, and the presence of lymphocytes in tumors is often associated with better clinical outcomes.^[1]^[2]

Adoptive cell transfer therapy

The use of TILs as an adoptive cell transfer therapy to treat cancer has been pioneered by Dr. Steven Rosenberg at the National Cancer Institute. Autologous lymphocytes are isolated from patients’ tumors and grown to very large numbers of cells in vitro. Prior to TIL treatment, patients are given nonmyeloablative chemotherapy to deplete native lymphocytes that can suppress tumor killing. Once lymphodepletion is completed, patients are then infused with TILs in combination with interleukin 2 (IL-2). Lion Biotechnologies is currently developing adoptive cell transfer with TILs for the treatment of cancer.

Melanoma

Several clinical trials have been conducted using TILs to treat patients with metastatic melanoma, a deadly form of skin cancer. Tumor reduction of 50% or more was observed in about half of melanoma patients treated with TILs.^[3]^[4]^[5]^[6] Some patients experienced complete responses with no detectable tumor remaining years after TIL treatment.^[7]

Other cancers

Clinical trials using TILs to treat digestive tract cancers, such as colorectal cancer,^[8] and cancers associated with the human papilloma virus (HPV), such as cervical cancer,^[9] are ongoing. Scientists are also investigating whether TILs can be used to treat other tumors, including lung, ovarian, bladder, and breast.

References

^ Vánky F, Klein E, Willems J et al. (1986). "Lysis of autologous tumor cells by blood lymphocytes tested at the time of surgery. Correlation with the postsurgical clinical course". Cancer Immunology, Immunotherapy 21 (1): 69–76. doi:10.1007/BF00199380. PMID 3455878.
^ Zhang L, Conejo-Garcia JR, Katsaros D et al. (January 2003). "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer". The New England Journal of Medicine 348 (3): 203–13. doi:10.1056/NEJMoa020177. PMID 12529460.
^ Dudley ME, Yang JC, Sherry R et al. (November 2008). "Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens". Journal of Clinical Oncology 26 (32): 5233–9. doi:10.1200/JCO.2008.16.5449. PMC 2652090. PMID 18809613.
^ Radvanyi LG, Bernatchez C, Zhang M et al. (December 2012). "Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients". Clinical Cancer Research 18 (24): 6758–70. doi:10.1158/1078-0432.CCR-12-1177. PMC 3525747. PMID 23032743.
^ Pilon-Thomas S, Kuhn L, Ellwanger S et al. (October 2012). "Efficacy of adoptive cell transfer of tumor-infiltrating lymphocytes after lymphopenia induction for metastatic melanoma". Journal of Immunotherapy 35 (8): 615–20. doi:10.1097/CJI.0b013e31826e8f5f. PMID 22996367.
^ Besser MJ, Shapira-Frommer R, Treves AJ et al. (May 2010). "Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients". Clinical Cancer Research 16 (9): 2646–55. doi:10.1158/1078-0432.CCR-10-0041. PMID 20406835.
^ Rosenberg SA, Yang JC, Sherry RM et al. (July 2011). "Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy". Clinical Cancer Research 17 (13): 4550–7. doi:10.1158/1078-0432.CCR-11-0116. PMC 3131487. PMID 21498393.
^ Clinical trial number NCT01174121 for "A Phase II Study Using Short-Term Cultured, CD8+-Enriched Autologous Tumor-infiltrating Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Digestive Tract Cancers" at ClinicalTrials.gov
^ Clinical trial number NCT01585428 for "A Phase II Study of Lymphodepletion Followed by Autologous Tumor-Infiltrating Lymphocytes and High-Dose Adesleukin for Human Papillomavirus-Associated Cancers" at ClinicalTrials.gov

External links

Lion Biotechnologies, Inc.

UpToDate Contents

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English Journal

Plaque-infiltrating T lymphocytes in patients with carotid atherosclerosis: an insight into the cellular mechanisms associated to plaque destabilization.

Profumo E, Buttari B, Tosti ME, Tagliani A, Capoano R, D'amati G, Businaro R, Salvati B, Riganò R.SourceDepartment of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy - rachele.rigano@iss.it.
The Journal of cardiovascular surgery.J Cardiovasc Surg (Torino).2013 Jun;54(3):349-57. Epub 2012 May 28.
Aim: Inflammation plays a crucial role in the progression of atherosclerotic plaques. The aim of the present study was to investigate phenotypic and functional characteristics of plaque-infiltrating T lymphocytes associated with a complicated phenotype of carotid atherosclerotic lesions. Methods: At
PMID 22669090

Immunomonitoring and prognostic relevance of neutrophils in clinical trials.

Donskov F.SourceDepartment of Oncology, Aarhus University Hospital, Denmark. Electronic address: fd@microbiology.au.dk.
Seminars in cancer biology.Semin Cancer Biol.2013 Jun;23(3):200-7. doi: 10.1016/j.semcancer.2013.02.001. Epub 2013 Feb 10.
The clinical relevance of the interaction between human cancer and neutrophils has recently begun to emerge. This review will focus on recently published articles regarding immunomonitoring of neutrophils in blood and tumor tissue in clinical trials comprising the main human tumor types, with a stro
PMID 23403174

Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the Hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival.

Yang RK, Kalogriopoulos NA, Rakhmilevich AL, Ranheim EA, Seo S, Kim K, Alderson KL, Gan J, Reisfeld RA, Gillies SD, Hank JA, Sondel PM.SourceThe Department of Human Oncology, University of Wisconsin, 4159 WIMR Bldg., 1111 Highland Ave, Madison, WI, 53705, USA.
Cancer immunology, immunotherapy : CII.Cancer Immunol Immunother.2013 May 10. [Epub ahead of print]
Hu14.18-IL2 is an immunocytokine (IC) consisting of human IL-2 linked to hu14.18 mAb, which recognizes GD2 disialoganglioside. Phase II clinical trials of intravenous-hu14.18-IL2 (IV-IC) in neuroblastoma and melanoma are underway, and have already demonstrated activity in neuroblastoma. In our Phase
PMID 23661160

Japanese Journal

Tumor-infiltrating lymphocytes and hepatocellular carcinoma : molecular biology

HIRAOKA Nobuyoshi
International journal of clinical oncology : official journal of the Japan Society of Clinical Oncology 15(6), 544-551, 2010-12-01
NAID 10027665099

NKG2D+CD4+ T Cells with Immune Suppressive Property Increase in Patients with Colorectal Cancer

Yamamoto Manabu,Saito Hiroaki,Kihara Kyoichi,Katano Kuniyuki,Ikeguchi Masahide
Yonago Acta medica 53(1), 9-16, 2010-3
… We examined NKG2D expression on both circulating and tumor infiltrating CD4+ and CD8+ T cells or NK cells and evaluated it by multicolor flow cytometry. … As a result, NKG2D expression on circulating and tumor-infiltrating CD8+ T cells and NK cells was downregulated in colorectal cancer patients. … On the other hand, circulating and tumor-infiltrating NKG2D+CD4+ T cells increased in colorectal cancer patients. …
NAID 120002003945