CXCR4-CXCL12-CXCR7, TLR2-TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients
A neoadjuvant clinical trial was previously conducted in patients with resectable colorectal cancer liver metastases (CRLM). At a median follow up of 28 months, 20/33 patients were dead of disease, 8 were alive with disease and 5 were alive with no evidence of disease. To shed further insight into biological features accounting for different outcomes, the expression of CXCR4-CXCL12-CXCR7, TLR2-TLR4, and the programmed death receptor-1 (PD-1)/programmed death-1 ligand (PD-L1) was evaluated in excised liver metastases. Expression profiles were assessed through qPCR in metastatic and unaffected liver tissue of 33 CRLM neoadjuvant-treated patients. CXCR4 and CXCR7, TLR2/TLR4, and PD-1/PD-L1 mRNA were significantly overexpressed in metastatic compared to unaffected liver tissues. CXCR4 protein was negative/low in 10/31, and high in 21/31, CXCR7 was negative/low in 16/31 and high in 15/31, CXCL12 was negative/low in 14/31 and high in 17/31 CRLM. PD-1 was negative in 19/30 and positive in 11/30, PD-L1 was negative/low in 24/30 and high in 6/30 CRLM. Stromal PD-L1 expression, affected the progression-free survival (PFS) in the CRLM population. Patients overexpressing CXCR4 experienced a worse PFS and cancer specific survival (CSS) (p = 0.001 and p = 0.0008); in these patients, KRAS mutation identified a subgroup with a significantly worse CSS (p < 0.01). Thus, CXCR4 and PD-L1 expression discriminate patients with the worse PFS within the CRLM evaluated patients. Within the CXCR4 high expressing patients carrying Mut-KRAS in CRLM identifies the worst prognostic group. Thus, CXCR4 targeting plus anti-PD-1 therapy should be explored to improve the prognosis of Mut-KRAS-high CXCR4-CRLMs.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2016 |
---|---|
Erschienen: |
2016 |
Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
---|---|
Enthalten in: |
Oncoimmunology - 5(2016), 12 vom: 07., Seite e1254313 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
D'Alterio, Crescenzo [VerfasserIn] |
---|
Links: |
---|
Themen: |
CXCR4–CXCL12–CXCR7 axis |
---|
Anmerkungen: |
Date Revised 30.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
---|
doi: |
10.1080/2162402X.2016.1254313 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM268349851 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM268349851 | ||
003 | DE-627 | ||
005 | 20231226193545.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231224s2016 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1080/2162402X.2016.1254313 |2 doi | |
028 | 5 | 2 | |a pubmed24n0894.xml |
035 | |a (DE-627)NLM268349851 | ||
035 | |a (NLM)28123896 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a D'Alterio, Crescenzo |e verfasserin |4 aut | |
245 | 1 | 0 | |a CXCR4-CXCL12-CXCR7, TLR2-TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients |
264 | 1 | |c 2016 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Revised 30.03.2022 | ||
500 | |a published: Electronic-eCollection | ||
500 | |a Citation Status PubMed-not-MEDLINE | ||
520 | |a A neoadjuvant clinical trial was previously conducted in patients with resectable colorectal cancer liver metastases (CRLM). At a median follow up of 28 months, 20/33 patients were dead of disease, 8 were alive with disease and 5 were alive with no evidence of disease. To shed further insight into biological features accounting for different outcomes, the expression of CXCR4-CXCL12-CXCR7, TLR2-TLR4, and the programmed death receptor-1 (PD-1)/programmed death-1 ligand (PD-L1) was evaluated in excised liver metastases. Expression profiles were assessed through qPCR in metastatic and unaffected liver tissue of 33 CRLM neoadjuvant-treated patients. CXCR4 and CXCR7, TLR2/TLR4, and PD-1/PD-L1 mRNA were significantly overexpressed in metastatic compared to unaffected liver tissues. CXCR4 protein was negative/low in 10/31, and high in 21/31, CXCR7 was negative/low in 16/31 and high in 15/31, CXCL12 was negative/low in 14/31 and high in 17/31 CRLM. PD-1 was negative in 19/30 and positive in 11/30, PD-L1 was negative/low in 24/30 and high in 6/30 CRLM. Stromal PD-L1 expression, affected the progression-free survival (PFS) in the CRLM population. Patients overexpressing CXCR4 experienced a worse PFS and cancer specific survival (CSS) (p = 0.001 and p = 0.0008); in these patients, KRAS mutation identified a subgroup with a significantly worse CSS (p < 0.01). Thus, CXCR4 and PD-L1 expression discriminate patients with the worse PFS within the CRLM evaluated patients. Within the CXCR4 high expressing patients carrying Mut-KRAS in CRLM identifies the worst prognostic group. Thus, CXCR4 targeting plus anti-PD-1 therapy should be explored to improve the prognosis of Mut-KRAS-high CXCR4-CRLMs | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CXCR4–CXCL12–CXCR7 axis | |
650 | 4 | |a KRAS mutation | |
650 | 4 | |a PD-1/PD-L1 | |
650 | 4 | |a colorectal cancer liver metastases (CRLM) | |
650 | 4 | |a toll-like receptors (TLRs) | |
700 | 1 | |a Nasti, Guglielmo |e verfasserin |4 aut | |
700 | 1 | |a Polimeno, Marianeve |e verfasserin |4 aut | |
700 | 1 | |a Ottaiano, Alessandro |e verfasserin |4 aut | |
700 | 1 | |a Conson, Manuel |e verfasserin |4 aut | |
700 | 1 | |a Circelli, Luisa |e verfasserin |4 aut | |
700 | 1 | |a Botti, Giovanni |e verfasserin |4 aut | |
700 | 1 | |a Scognamiglio, Giosuè |e verfasserin |4 aut | |
700 | 1 | |a Santagata, Sara |e verfasserin |4 aut | |
700 | 1 | |a De Divitiis, Chiara |e verfasserin |4 aut | |
700 | 1 | |a Nappi, Anna |e verfasserin |4 aut | |
700 | 1 | |a Napolitano, Maria |e verfasserin |4 aut | |
700 | 1 | |a Tatangelo, Fabiana |e verfasserin |4 aut | |
700 | 1 | |a Pacelli, Roberto |e verfasserin |4 aut | |
700 | 1 | |a Izzo, Francesco |e verfasserin |4 aut | |
700 | 1 | |a Vuttariello, Emilia |e verfasserin |4 aut | |
700 | 1 | |a Botti, Gerardo |e verfasserin |4 aut | |
700 | 1 | |a Scala, Stefania |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Oncoimmunology |d 2012 |g 5(2016), 12 vom: 07., Seite e1254313 |w (DE-627)NLM218817029 |x 2162-402X |7 nnns |
773 | 1 | 8 | |g volume:5 |g year:2016 |g number:12 |g day:07 |g pages:e1254313 |
856 | 4 | 0 | |u http://dx.doi.org/10.1080/2162402X.2016.1254313 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 5 |j 2016 |e 12 |b 07 |h e1254313 |