Colorectal cancer

* innate immunity - epithelial cells - sentinel cells in tissues [phagocytes (neutrophils, monocytes/macrophages), dendritic cells, mast cells, etc.] - innate lymphoid cells (ILCs) (NK cells, etc.) - plasma proteins (complements, etc.) * ILCs - Th1 - Th2 - Th17 * Lymphocytes B lymphocytes : produces antibodies "humoral immunity" : mature in the BM T lymphocytes:   "cell-mediated immunity" : mature in the thymus - CD4+ T cells helper T cells: help (1) B cells to produces antibodies, and help (2) phagocytes to destroy ingested microbes regulatory T cells (some): prevent/limit the immune response - CD8+ T cells (=cytotoxic T lymphocytes, CTLs): kill cells harboring intracellular microbes * interferon: a subgroup of cytokines (원래 viral infection에 방해하는 것으로 알려져 있었으나, 중요한 immunomodulatory function을 가진다) - type I (interferon-alpha and -beta): the main function is to prevent viral replication -  type II (=interferon-gamma) :  macrophages

기본적으로 종양은 inflamed와 non-inflamed로 구분됨. 1. inflamed (preexisting antitumor immune response) TIL high IFN-gamma producing CD8+ T cells PD-L1 in tumor-infiltrating immune cells. possible genome instability (high mutational burden) 2. non-inflamed TIL low  PD-L1 (-) 예) 소아암이 single gene mutation driver에 의해서 driven되는 noninflamed tuor의 대표적인 예임.

Cre (from “Cre”ates) recombinase: - P1 bacteriophage에서 나온 enzyme임 - Substrate DNA에 결합하여, - 2개의 LoxP sites 사이를 cut out하도록 디자인되었음.. LoxP (from “L”ocus “O”f “X”-over in “P”1 bacteriophage) - P1 bacteriophage에 있는 34 bp region ( ATAAC TTCGT ATA GC ATACA T TATA CGAAG TTAT ) 으로 2개의 symmetric한 13bp sequence를 포함함. - asymmetric 8 bp region때문에 Cre가 deletion, inversion, translocation을 catalyze 하게 됨.

http://investors.foundationmedicine.com/releasedetail.cfm?releaseid=1062384 FoundationOne CDx - first US FDA-approved CGP assay for all solid tumors - offered as a nationally covered benefit across all solid tumors for Medicare and Medicare Advantage beneficiaries   https://www.medscape.com/viewarticle/894190 - technical information  https://assets.ctfassets.net/vhribv12lmne/6Rt6csmCPuaguuqmgi2iY8/e3a9b0456ed71a55d2e4480374695d95/FoundationOne_CDx.pdf

1. NCCN Guidelines on Management of Immunotherapy-Related Toxicities : 미국 NCCN 가이드라인으로, immunotherapy에 관해서는 2018년에 처음으로 나옴 https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf 2. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline : 미국 임상종양학회 (ASCO) 가이드라인 (2018) http://ascopubs.org/doi/abs/10.1200/JCO.2017.77.6385 3. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up : 유럽 종양학회 (ESMO) 가이드라인 (2017) https://academic.oup.com/annonc/article/28/suppl_4/iv119/3958159 4. 간호사 및 환자들을 위한 자료 https://www.ons.org/practice-resources/cancer-therapies/immunotherapy-resources

TCGA, NHGRI, NCI는 그동안 33개 암종 의 genomic map을 만들었음. Pan-Cancer Atlas 와 관련된 25개의 TCGA 논문이 이번 주에 5개 저널에 출판될 예정이며, 이 논문이 첫 번째임. Liu Y, Sethi NS, Hinoue T, Schneider BG et al. 교신저자: Thorsson V (Institute for Systems Biology), Bass AJ (Harvard), Laird PW (Van Andel Research Institute) http://www.cell.com/cancer-cell/fulltext/S1535-6108(18)30114-4 Methods: Esophagus, stomach, colon/rectum의 921개 adenoca.를 분석 Results 1) GI adenoca.는 5개의 molecular subtypes으로 구분됨 (EBV, MSI, HM-SNV, CIN, GS) 2) Hypermutated tumors는 암종에 관계없이 distinct ( MSI , HM-SNV ) 3) CIN은 다양한 형태로 나타나며, upper (esophagus, stomach)이 더 focal한 CNV를 보임 4) Colon/rectum 중 hypermuation이나 aneuplody가 낮은, genome-stable CRC group은 DNA hypermethylation  + KRAS/SOX9/PCBNP1 mutation 이 enrich됨.