A high density of PD-L1-expressing immune cells is significantly correlated with favorable disease free survival in nonmetastatic colorectal cancer

Abstract

The impact of immune cells (ICs) expressing various markers remains poorly understood in nonmetastatic colorectal cancer patients who have undergone colectomy. Here, we aimed to clarify the correlation between IC density and clinical parameters and survival. Programmed death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), clusters of differentiation (CD)-3, CD-8, and CD45RO immunostaining was performed for 421 patients using tissue microarray and automatic counting. Tumor stroma area immune density was assessed in comparison to clinical histological factors and surgical outcomes. High-density CD-8 expression was significantly associated with current smoking habits or a smoking history ( P = .006). High-density of PD-1 expression was correlated with Lynch syndrome patients ( P < .001) and with patients who did not consume alcohol ( P = .034). A significant decrease in CR45RO expression density was associated with aging ( P = .002 and r = –0.014), and high-density CD-3, CD-8, and PD-1 expression was significantly associated with right colon tumor location ( P < .001). High CD-3 and PD-L1 expression was significantly associated with early tumor T-staging ( P = .018 and P = .002). High-density PD-1 expression was significantly correlated with mucinous type adenocarcinoma ( P = .027) and poor differentiation ( P < .001). For treatment outcomes, multivariate analysis confirmed that patients exhibiting high-density PD-L1 expression possessed significantly longer disease free survival (adjusted hazard ratio: 0.752, 95% confidence interval [CI]: 0.61–0.92, P = .006) and overall survival (adjusted hazard ratio: 0.872, 95% CI: 0.75–1.91, P = .064) Significantly varied density in IC subsets was related to distinct demographic or clinic-histological factors. The presence of high-density PD-L1-expressing ICs is an independent favorable prognostic factor for disease free survival and overall survival among stage I to III colorectal cancer patients.

PD-L1 Expression in High-Risk Early-Stage Colorectal Cancer—Its Clinical and Biological Significance in Immune Microenvironment

“…Although the prognostic value of PD-L1 expression remains inconclusive, several studies have reported that PD-L1 expression is an important prognostic factor of CRC. Recent studies have demonstrated that higher PD-L1 expression on immune cells in the TME is correlated with better survival outcomes in early-stage CRC [ 6 , 8 , 9 , 33 ]. On the contrary, some clinical studies have reported that prominent PD-L1 expression on tumor cells indicates poorer survival outcomes of CRC.…”

“…The PD-L1/PD-1 pathway downregulates T-cell function during inflammatory states and takes part in adaptive immune resistance in cancer [ 5 ]. PD-L1 expression has a prognostic value in various types of cancer [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]; however, its significance in early-stage CRCs is still debated. The inconsistent results are probably from the heterogeneity of the study population, different PD-L1 staining antibodies, different definitions of PD-L1 positivity, etc.…”

Low PD‐L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment

“…It should also be noted that the translation of these results into daily practice is hampered by the different scores used for PD‐L1 evaluation [i.e. tumour proportion score (TPS), 18 combined positive score (CPS) 21 or immune cell score (ICS) 19 ], contributing to partially conflicting results 22,23 …”

“…20 It should also be noted that the translation of these results into daily practice is hampered by the different scores used for PD-L1 evaluation [i.e. tumour proportion score (TPS), 18 combined positive score (CPS) 21 or immune cell score (ICS) 19 ], contributing to partially conflicting results. 22,23 Based on this background, PD-L1 expression could represent a surrogate marker of tumour aggressiveness and therefore be associated with nodal metastasis in pT1 CRC.…”

“…[9][10][11][12][13][14] In this context, some recent studies have suggested a possible relationship between programmed death ligand 1/CD274 (PD-L1) expression and prognosis in CRCs. [15][16][17][18] Specifically, it has been demonstrated that higher expression of PD-L1 in tumour infiltrating immune cells imparts a better prognosis in different CRC stages, 19 but this association has not been specifically tested in the subset of early invasive lesions. 20 It should also be noted that the translation of these results into daily practice is hampered by the different scores used for PD-L1 evaluation [i.e.…”