Проучванията в областта на противотуморната имунотерапия се развиват в посока на по-насочени стратегии
Откритията в изследванията на имунната система са помогнали за усъвършенстването на имунотерапевтичните стратегии към по-насочени.1,2
Разработване на по-персонализиран подход в изследванията на противотуморната имунотерапия
С развитието на по-насочените стратегии, изследванията се фокусират върху идентифицирането на предиктори на индивидуален имунен отговор чрез специфични туморни характеристики и фактори в туморната микросреда, като:
- Наличието на имунни клетки, инфилтриращи тумора8
- Способността на имунните клетки да инфилтрират туморната микросреда може да бъде основен критерий за различни имунно-насочени терапии, и може да определи кои тумори по-вероятно ще отговорят.
- Модели на генна експресия в туморите, особено гени, участващи в имунния отговор9
- Протеинова експресия на клетъчната повърхност
- PD-L1 експресия на туморните клетки и имунни клетки, инфилтриращи туморите10,11
- MUC1 експресия на туморните клетки12
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Референции:
- Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1-10. PMID: 23890059
- Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011;480:480-489. PMID: 22193102
- Lesterhuis WJ, Haanen JB, Punt CJ. Cancer immunotherapy—revisited. Nat Rev Drug Discov. 2011;10:591-600. PMID: 21804596
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01494688. Accessed March 4, 2015.
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT00739609. Accessed March 4, 2015.
- Glienke W, Esser R, Priesner C, et al. Advantages and applications of CAR-expressing natural killer cells. Front Pharmacol. 2015;6:21. doi: 10.3389/fphar.2015.00021. PMID: 25729364
- National Institutes of Health ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01303705. Accessed March 4, 2015.
- Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumour microenvironment. Nat Immunol. 2013;14:1014-1022.PMID: 24048123
- Ji RR, Chasalow SD, Wang L, et al. An immune-active tumour microenvironment favors clinical response to ipilimumab. Cancer Immunol Immunother. 2012;61:1019-1031. PMID: 22146893
- Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4:127ra37. PMID: 22461641
- Chen DS, Irving BA, Hodi FS. Molecular pathways: next-generation immunotherapy—inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res. 2012;18:6580-6587. PMID: 23087408
- Stojnev S, Ristic-Petrovic A, Velickovic LJ, et al. Prognostic significance of mucin expression in urothelial bladder cancer. Int J Clin Exp Pathol. 2014;7:4945-4958. PMID: 25197366
- Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-264. PMID: 22437870
- Taylor RC, Patel A, Panageas KS, Busam KJ, Brady MS. Tumour-infiltrating lymphocytes predict sentinel lymph node positivity in patients with cutaneous melanoma. J Clin Oncol. 2007;25:869-875. PMID: 17327608
- Hiraoka K, Miyamoto M, Cho Y, et al. Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer. 2006;94:275-280. PMID: 16421594
- Sharma P, Shen Y, Wen S, et al. CD8 tumour-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma.Proc Natl Acad Sci U S A. 2007;104:3967-3972. PMID: 17360461
- Okita Y, Tanaka H, Ohira M, et al. Role of tumour-infiltrating CD11b+ antigen-presenting cells in the progression of gastric cancer. J Surg Res. 2014;186:192-200. PMID: 24120241
- Matsuda S, Yamane T, Hamaji M. CD4- and TCRalphabeta-positive T lymphocytes predominantly infiltrated into well-moderately differentiated colon adenocarcinoma tissues. Jpn J Clin Oncol. 1998;28:97-103. PMID: 9544823
- Gao Q, Wang XY, Qiu SJ, et al. Overexpression of PD-L1 significantly associates with tumour aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15:971-979. PMID: 19188168
- Badoual C, Hans S, Rodriguez J, et al. Prognostic value of tumour-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006;12:465-472. PMID: 16428488
- Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumour-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007;13:1757-1761. PMID: 17363529
- Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumour microenvironment of patients with pancreas or breast adenocarcinoma. J lmmunol. 2002;169:2756-2761. PMID: 12193750
- Noonan K, Matsui W, Serafini P, et al. Activated marrow-infiltrating lymphocytes effectively target plasma cells and their clonogenic precursors. Cancer Res. 2005;65:2026-2034. PMID: 15753403
- Chen BJ, Chapuy B, Ouyang J, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19:3462-3473. PMID: 23674495