Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer

Enkhbat, Tumenjin; Nishi, Masaaki; Takasu, Chie; Yoshikawa, Kozo; Higashijima, Jun; Tokunaga, Takuya; Kashihara, Hideya; Ishikawa, Daichi; Shimada, Mitsuo

doi:10.21873/anticanres.12603

Cited by 53 publications

(62 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our results are consistent with those of Huang et al [7], who demonstrated that high PD-L1 expression on tumour cells Cases with no clinical information or for which the data are not assessable due to cautery artifact, fragmentation, or incorrect orientation of tumour tissues are excluded in statistical analyses was associated with improved disease-free survival and overall survival. Some studies [8][9][10] indicated that PD-L1-positive immunoreactivity on tumour cells was a significant predictor of unfavourable overall, disease-free, or recurrence-free survival in colorectal adenocarcinoma. However, other studies [11,12] reported that PD-L1 expression in tumour cells was not associated with clinical prognosis, regardless of MSI.…”

Section: Discussionmentioning

confidence: 99%

“…In colorectal adenocarcinoma, PD-L1 or PD-1 expression, tumour mutational burden (TMB), tumour-infiltrating lymphocytes (TIL), and microsatellite instability (MSI) have been accepted as fundamental biomarkers that guide the clinical application of immune checkpoint inhibitors based on the following lines of evidence [6]: 1) PD-L1 expression is significantly associated with favourable [7] or unfavourable [8][9][10] prognostic values except some studies [11,12], and blocking PD-L1/PD-1 interaction can prolong tumour suppression and stabilize the progression of advanced cancers [13]; 2) the response rate to immune checkpoint inhibitors is significantly associated with increased tumour mutation burden [14]; 3) PD-L1-positive tumour cells and CD8-positive TIL are key prognostic biomarkers for locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy [15]; 4) MSI is significantly associated with a prolonged response rates and favourable clinical outcomes in colorectal and non-colorectal cancer patients treated with immune checkpoint inhibitors [16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma

2020

View full text Add to dashboard Cite

Background: Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancerrelated death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapytargetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup. Methods: Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and deficient mismatch repair (dMMR) were performed and evaluated. Results: Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with dMMR status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression. Conclusions: TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma

2020

View full text Add to dashboard Cite

show abstract

“…Our results are consistent with those of Huang et al [7], who demonstrated that high PD-L1 expression on tumour cells was associated with improved disease-free survival and overall survival. Some studies [8][9][10] indicated that PD-L1-positive immunoreactivity on tumour cells was a significant predictor of unfavourable overall, disease-free, or recurrence-free survival in colorectal adenocarcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…In colorectal adenocarcinoma, PD-L1 or PD-1 expression, tumour mutational burden (TMB), tumourinfiltrating lymphocytes (TIL), and microsatellite instability (MSI) have been accepted as fundamental biomarkers that guide the clinical application of immune checkpoint inhibitors based on the following lines of evidence [6]: 1) PD-L1 expression is significantly associated with favourable [7] or unfavourable [8][9][10] prognostic values except some studies [11,12], and blocking PD-L1/PD-1 interaction can prolong tumour suppression and stabilize the progression of advanced cancers [13]; 2) the response rate to immune checkpoint inhibitors is significantly associated with increased tumour mutation burden [14]; 3) PD-L1-positive tumour cells and CD8-positive TIL are key prognostic biomarkers for locally advanced rectal cancer patients treated with neoadjuvant chemoradiotherapy [15]; 4) MSI is significantly associated with a prolonged response rates and favourable clinical outcomes in colorectal and non-colorectal cancer patients treated with immune checkpoint inhibitors [16].…”

Section: Introductionmentioning

confidence: 99%

Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma

Noh

Kwak

Eom

2020

Preprint

View full text Add to dashboard Cite

Background Colorectal adenocarcinoma is the third most common cancer worldwide and a leading cause of cancer-related death. The recent emergence of diverse immunotherapeutic agents has made it crucial to interpret a complex tumour microenvironment intermingled with tumour-infiltrating immune cells to predict the immunotherapeutic response rate. However, in colorectal adenocarcinoma, studies are lacking that provide detailed analyses of programmed death-ligand 1 (PD-L1) and tumour-infiltrating lymphocytes (TIL) to elucidate their prognostic values and to identify immunotherapy-targetable subgroups, preferably with multiple immune-related biomarkers. In the present study, we categorize colorectal adenocarcinomas into four types of tumour immune microenvironments according to PD-L1 expression and TIL, analyse their prognostic values, and propose an immunotherapy-targetable subgroup.Methods Formalin-fixed, paraffin-embedded tissue samples of surgically resected primary colorectal adenocarcinomas (n = 489) were obtained and arrayed on tissue microarray blocks. Immunohistochemical stains for PD-L1, programmed cell death protein 1 (PD-1), cluster of differentiation 8 (CD8), and microsatellite instability (MSI) were performed and evaluated.Results Tumour microenvironment immune type (TMIT) I (PD-L1-positive tumour cells and CD8-high TIL) and type II (PD-L1-negative tumour cells and CD8-low TIL) showed the best and worst prognoses, respectively. PD-L1 overexpression was significantly associated with MSI status. PD-L1 immunoreactivity was positively correlated with TIL having CD8 or PD-1 overexpression.Conclusions TMIT I subgroup showed stronger CD8/PD-L1/PD-1 signalling interaction compared to the other TMIT. Therefore, we propose that the TMIT I subgroup is a candidate TMIT to predict effective response rate for existing immune checkpoint inhibitors and determine targetable subgroups for emerging therapies.

show abstract

“…Dowiedziono również, że czas przeżycia jest krótszy w porównaniu z chorymi, u których ekspresji PDL1 nie stwierdzono[114]. Ekspresja PDL1 wpływała negatywnie na wartości OS oraz DFS chorych na raka jelita grubego, gdyż 5letni OS przy obecności ligandu wynosił 76,7% oraz 93,2% przy braku PDL1, z kolei w przypadku DFS było to odpowiednio 69,7% i 83,3%[115]. W przypadku HCC ekspresja PDL1 na komórkach nowotworowych związana jest z niekorzystnym rokowaniem oraz może stanowić marker do oceny ryzyka nawrotu choroby, które w przypadku ekspresji PDL1 było niemal dwukrotnie wyższe[55,116].…”

unclassified

Immunoterapia z użyciem przeciwciał monoklonalnych ukierunkowanych na szlak PD-1/PD-L1 w chorobach nowotworowych

Malesa

Nowak

Skórka

et al. 2018

Acta Haematologica Polonica

View full text Add to dashboard Cite

WSTĘP Badania ostatnich lat w dużym stopniu koncentrują się na poszukiwaniu i doskonaleniu nowych metod leczenia chorób nowotworowych. Jedną z obiecujących metod jest immunoterapia, która opiera się na pobudzeniu i wzmocnieniu odpowiedzi układu immunologicznego do walki z komórkami nowotworowymi. Immunoterapię można podzielić na swoistą, ukierunkowaną na ściśle określony rodzaj komórek, które mają być niszczone, oraz nieswoistą, aktywującą różne mechanizmy odpowiedzi układu odpornościowego. Obecnie najczęściej wykorzystywaną metodą immunoterapii nowotworów jest stosowanie przeciwciał monoklonalnych. Przeciwciała monoklonalne mogą być skierowane przeciwko swoistym antygenom nowotworowym lub przeciwko cząsteczkom modulującym odpowiedź immunologiczną, powodując jej nasilenie. Dodatkowo, przeciwciała monoklonalne mogą również hamować rozwój nowotworu przez blokowanie czynników niezbędnych do jego wzrostu [1, 2]. Wśród mechanizmów determinujących aktywność przeciw nowotworową przeciwciał rozpoznających antygeny nowotworowe wyróżnia się mechanizmy bezpośrednie oraz pośrednie. Mechanizmy bezpośrednie obejmują przede wszystkim aktywację apoptozy lub zahamowanie szlaków transdukcji sygnału przez związanie receptorów błonowych na powierzchni komórek nowotworowych. Natomiast do grupy mechanizmów pośrednich należą cytotoksyczność zależna od przeciwciał (antibodydependent cellular cytotoxicity -ADCC) i cytotoksyczność zależna od dopełniacza (complement-dependent cytotoxicity -CDC). Istnieje również grupa przeciwciał ukierunkowanych na określone białka supresorowe stanowiące negatywne punkty kontrolne na powierzchni komórek immunologicznych lub eliminujące białka regulatorowe obecne w mikrośrodowisku nowotworu [3]. Immunoterapia z użyciem przeciwciał monoklonalnych ukierunkowanych na szlak PD-1/PD-L1 w chorobach nowotworowych Monoclonal antibodies against PD-1/PD-L1 pathway StreszczenieKomórki nowotworowe modyfikują aktywność układu odpornościowego, wyciszając jego reakcję na rozwijający się nowotwór. Jednym z głównych szlaków prowadzących do wyciszenia aktywności limfocytów jest szlak PD-1/PD-L1, zatem jest jednym z głównych celów immunoterapii. Blokowanie PD-1 lub PD-L1 przy pomocy przeciwciał monoklonalnych umożliwia przywrócenie aktywności układu odpornościowego i wstrzymanie bądź cofnięcie choroby. W badaniach klinicznych określano skuteczność i bezpieczeństwo terapii przy użyciu przeciwciał anty-PD-1 oraz anty-PD-L1 w nowotworach litych oraz hematologicznych. Obiecujące wyniki badań, w monoterapii lub połączeniu z chemio-lub radioterapią, prowadzą do rejestracji terapii przeciwciał monoklonalnych anty-PD-1 i anty-PD-L1 w coraz większej liczbie chorych onkologicznych. AbstractCancer cells can modify activity of immune system, decreasing its response to ongoing disease progression. One of main pathways leading to the T-cell exhaustion is PD-1/PD-L1 pathway, so it became one of main targets of modern immunotherapy. Blocking PD-1 or PD-L1 with monoclonal antibodies leads to restoration of immune system activity and inhibits ...

show abstract

Programmed Cell Death Ligand 1 Expression Is an Independent Prognostic Factor in Colorectal Cancer

Abstract: PD-1 and PD-L1 expressions were associated with a poor prognosis and correlated with TGF-β and Foxp3 expressions in patients with CRC.

Cited by 53 publications

References 31 publications

Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma

Immune classification for the PD-L1 expression and tumour-infiltrating lymphocytes in colorectal adenocarcinoma

Immune Classification for the PD-L1 Expression and Tumour-Infiltrating Lymphocytes in Colorectal Adenocarcinoma

Immunoterapia z użyciem przeciwciał monoklonalnych ukierunkowanych na szlak PD-1/PD-L1 w chorobach nowotworowych

Contact Info

Product

Resources

About