Cytolytic Activity Score to Assess Anticancer Immunity in Colorectal Cancer

Annals of Surgical Oncology
Sumana NarayananKazuaki Takabe

Abstract

Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA). CYT was defined by GZMA and PRF1 expression, and CIBERSORT was used to evaluate intratumoral immune cell composition. High CYT was associated with high microsatellite instability (MSI-H), as well as high levels of activated memory CD4+T cells, gamma-delta T cells, and M1 macrophages. CYT-high CRC patients had improved overall survival (p = 0.019) and disease-free survival (p = 0.016) compared with CYT-low CRC patients, especially in TIL-positive tumors. Multivariate analysis demonstrated that CYT- high associates with improved survival independently after controlling for age, lymphovascular invasion, colonic location, microsatellite instability, and TIL positivity. The levels of immune checkpoint molecules (ICMs)-programmed death-1 (PD-1), programmed deat...Continue Reading

References

Jun 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Qiang GaoZhao-You Tang
Dec 10, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul SalamaBarry Iacopetta
Mar 25, 2010·Immunology·Megan K L MacLeodPhilippa Marrack
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Sep 27, 2012·Annals of Surgical Oncology·Steven C KatzRonald P DeMatteo
Sep 28, 2013·Nature Genetics·UNKNOWN Cancer Genome Atlas Research NetworkJoshua M Stuart
May 6, 2014·Cancer Immunology Research·Ana C Anderson
Mar 31, 2015·Nature Methods·Aaron M NewmanAsh A Alizadeh
Jun 2, 2015·The New England Journal of Medicine·Dung T LeLuis A Diaz
Jun 13, 2015·The Oncologist·Gregory K Pennock, Laura Q M Chow
Dec 26, 2015·Nucleic Acids Research·Antonio ColapricoHoutan Noushmehr
Mar 24, 2016·Oncotarget·Young Kwang ChaeFrancis J Giles
Apr 14, 2016·International Journal of Cancer. Journal International Du Cancer·Jonna BerntssonKarin Jirström
Oct 28, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Lik Hang LeeJinru Shia
Nov 1, 2016·Nature Medicine·Ronald J HauseStephen J Salipante
Oct 21, 2016·Cell Reports·Marios GiannakisLevi A Garraway
Dec 23, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David BalliRobert H Vonderheide
Jan 8, 2017·Breast Cancer Research and Treatment·Rajesh RamanathanKazuaki Takabe
Jan 21, 2017·International Journal of Molecular Sciences·Inés MármolMaría Jesús Rodriguez Yoldi
Jan 22, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Valeria GovernaGiulio C Spagnoli
Mar 4, 2017·Cancer Immunology Research·Andrew R GreenSrinivasan Madhusudan
Apr 6, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Hongxia YanHongjun Fu
Dec 5, 2017·Molecular Therapy. Methods & Clinical Development·Daniel J WoodsworthRobert A Holt
Jan 23, 2018·Immunology·Kayla A HolderMichael D Grant

❮ Previous
Next ❯

Citations

Oct 28, 2018·Annals of Surgical Oncology·Tsutomu KawaguchiKazuaki Takabe
Oct 1, 2019·The International Journal of Biological Markers·Huihua CaoQicheng Lu
Aug 21, 2019·Journal of Experimental & Clinical Cancer Research : CR·Apostolos ZaravinosGeorgios D Ayiomamitis
Aug 26, 2020·Immunological Reviews·Toshiyasu SuzukiSeth B Coffelt
May 31, 2020·Annals of Surgical Oncology·Hideo TakahashiKazuaki Takabe
May 3, 2020·International Journal of Molecular Sciences·Yoshihisa TokumaruKazuaki Takabe
Apr 26, 2020·International Journal of Molecular Sciences·Masanori OshiKazuaki Takabe
Sep 26, 2020·International Journal of Molecular Sciences·Masanori OshiKazuaki Takabe
Jul 8, 2020·International Journal of Molecular Sciences·Shipra GandhiKazuaki Takabe
Sep 29, 2020·Cancer Biomarkers : Section a of Disease Markers·Qingwen ZengZhengrong Li
Apr 10, 2019·Annals of Surgical Oncology·Kerry-Ann McDonaldKazuaki Takabe
May 22, 2020·Annals of Surgical Oncology·Hideo TakahashiKazuaki Takabe
Mar 7, 2021·International Journal of Molecular Sciences·Mohammed H AbuwarwarAnne L Fletcher
Apr 5, 2021·International Immunopharmacology·Yuansheng ZhengWei Jiang
Oct 8, 2021·Frontiers in Cell and Developmental Biology·Zuobing ChenXiaosheng Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Cancer Genomics (Keystone)

Cancer genomics approaches employ high-throughput technologies to identify the complete catalog of somatic alterations that characterize the genome, transcriptome and epigenome of cohorts of tumor samples. Discover the latest research using such technologies in this feed.