TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer.
<h4>Background</h4>Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers pat...
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2010
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oai:doaj.org-article:9e52c81e1a5e42c096360efe9bddb2082021-11-18T07:01:50ZTIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer.1932-620310.1371/journal.pone.0014282https://doaj.org/article/9e52c81e1a5e42c096360efe9bddb2082010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21179245/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed.<h4>Methodology/principal findings</h4>Colorectal cancers from a test (n=1197) and external validation (n=209) cohort of MMR-proficient colorectal cancers were mounted onto single and multiple punch tissue microarrays. Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8, CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh colorectal cancer specimens using specific cell population markers were performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p=0.029), CD8+ (p<0.001), CD45RO+ (p=0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+ (p=0.035), MUM1+ (p=0.014), PD1+ (p=0.034) and TIA-1+ TILs (p<0.001) were linked to favourable outcome. Adjusting for age, gender, TNM stage and post-operative therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001; HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results were confirmed on the validation cohort (p=0.006). TIA-1+ cells were mostly CD8+ (57%), but also stained for TCRγδ (22%), CD66b (13%) and only rarely for CD4+, macrophage and NK cell markers.<h4>Conclusions</h4>TIA-1 adds prognostic information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA-1+ which translates into improved risk stratification for approximately 35% of all patients with MMR-proficient colorectal cancers.Inti ZlobecEva KaramitopoulouLuigi TerraccianoSalvatore PiscuoglioGiandomenica IezziManuele Giuseppe MuraroGiulio SpagnoliKristi BakerAlexandar TzankovAlessandro LugliPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e14282 (2010) |
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DOAJ |
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| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Inti Zlobec Eva Karamitopoulou Luigi Terracciano Salvatore Piscuoglio Giandomenica Iezzi Manuele Giuseppe Muraro Giulio Spagnoli Kristi Baker Alexandar Tzankov Alessandro Lugli TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| description |
<h4>Background</h4>Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed.<h4>Methodology/principal findings</h4>Colorectal cancers from a test (n=1197) and external validation (n=209) cohort of MMR-proficient colorectal cancers were mounted onto single and multiple punch tissue microarrays. Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8, CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh colorectal cancer specimens using specific cell population markers were performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p=0.029), CD8+ (p<0.001), CD45RO+ (p=0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+ (p=0.035), MUM1+ (p=0.014), PD1+ (p=0.034) and TIA-1+ TILs (p<0.001) were linked to favourable outcome. Adjusting for age, gender, TNM stage and post-operative therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001; HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results were confirmed on the validation cohort (p=0.006). TIA-1+ cells were mostly CD8+ (57%), but also stained for TCRγδ (22%), CD66b (13%) and only rarely for CD4+, macrophage and NK cell markers.<h4>Conclusions</h4>TIA-1 adds prognostic information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA-1+ which translates into improved risk stratification for approximately 35% of all patients with MMR-proficient colorectal cancers. |
| format |
article |
| author |
Inti Zlobec Eva Karamitopoulou Luigi Terracciano Salvatore Piscuoglio Giandomenica Iezzi Manuele Giuseppe Muraro Giulio Spagnoli Kristi Baker Alexandar Tzankov Alessandro Lugli |
| author_facet |
Inti Zlobec Eva Karamitopoulou Luigi Terracciano Salvatore Piscuoglio Giandomenica Iezzi Manuele Giuseppe Muraro Giulio Spagnoli Kristi Baker Alexandar Tzankov Alessandro Lugli |
| author_sort |
Inti Zlobec |
| title |
TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| title_short |
TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| title_full |
TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| title_fullStr |
TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| title_full_unstemmed |
TIA-1 cytotoxic granule-associated RNA binding protein improves the prognostic performance of CD8 in mismatch repair-proficient colorectal cancer. |
| title_sort |
tia-1 cytotoxic granule-associated rna binding protein improves the prognostic performance of cd8 in mismatch repair-proficient colorectal cancer. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/9e52c81e1a5e42c096360efe9bddb208 |
| work_keys_str_mv |
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| _version_ |
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