PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer

Badoual, Cécile; Hans, Stéphane; Merillon, Nathalie; Ryswick, Cordélia Van; Ravel, Patrice; Benhamouda, Nadine; Levionnois, Emeline; Nizard, Mevyn; Si-Mohamed, Ali; Besnier, Nicolas; Gey, Alain; Rotem-Yehudar, Rinat; Péré, Hélène; Tran, Thi; Guerin, Coralie L.; Chauvat, Anne; Dransart, Estelle; Alanio, Cécile; Albert, Sébastien; Barry, B.; Sandoval, Fédérico; Quintin-Colonna, Françoise; Bruneval, Patrick; Fridman, Wolf‐Herman; Lemoine, François M.; Oudard, Stéphane; Johannes, Ludger; Olive, Daniel; Brasnu, Daniel; Tartour, Éric

doi:10.1158/0008-5472.can-12-2606

Cited by 557 publications

(489 citation statements)

References 52 publications

(76 reference statements)

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“…cell density in the tumor microenvironment also appeared to be related to survival outcomes, although there was no statistical significance (Fig. 2g, h); this finding is similar to that of a previous study, in which PD-1-expressing tumor-infiltrating T cells were a favorable prognostic biomarker in head and neck cancer [36]. In summary, our study reveals that immunosuppressive proteins are expressed in some patients with GC, and that these patients have distinct clinicopathological characteristics.…”

Section: Discussionsupporting

confidence: 88%

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

et al. 2014

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Background There are few data on the clinical implications of immunosuppressive protein expression in tumors and immune cell infiltration within the tumor microenvironment in patients with gastric cancer (GC). Methods In this study, 243 patients with curatively resected GC were included. The levels of immunosuppressive protein expression [programmed cell death 1 ligand 1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and indoleamine 2,3-dioxygenase (IDO)] in tumors and the densities of immune cells [CD3(?), CD4(?), CD8(?), or PD-1(?) cells] within the tumor microenvironment were measured using immunohistochemical analysis. Results Positive PD-L1, CTLA-4, and IDO expression was observed in 43.6, 65.8, and 47.7 % of the patients, respectively. Expression of PD-L1, CTLA-4, and IDO was related to less advanced stage, intestinal type, and well/ moderately differentiated adenocarcinoma (P \ 0.05). PD-L1 expression was related to better disease-free survival (DFS) and overall survival (OS) in GC [PD-L1(?) vs. PD-L1(-) tumors: 5-year DFS rate, 82.6 vs. 66.9 %; 5-year OS rate, 83.0 vs. 69.1 % (P values \0.05)]. Survival outcomes were also better in patients with a higher density of CD3(?) cells within the tumor microenvironment than in those with a lower density of CD3(?) cells [5-year DFS rate, 80.9 vs. 67.0 %; 5-year OS rate, 82.5 vs. 68.0 % (P values \0.05)]. In multivariate analysis, these two immune markers had a prognostic impact on survival, independent of other clinical variables. Conclusions GC patients with immunosuppressive protein expression (PD-L1, CTLA-4, or IDO) had distinct clinicopathological characteristics. PD-L1(?) expression and a high-CD3 tumor microenvironment are favorable prognostic markers in GC.

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Section: Discussionsupporting

confidence: 88%

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

et al. 2014

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“…[45][46][47][48] These studies suggested that increased PD-1 + tumor-infiltrating lymphocytes may reflect a subset of immune cells previously activated by the antitumor immune response, and thereby correlated with a favorable clinical outcome. 48 However, PD-1 + T cells have been regarded as functionally exhausted rather than activated because of chronic and persistent antigenic exposure from either viral infection or the tumor microenvironment, suggesting that the PD-1 + /CD8 + tumor-infiltrating lymphocyte ratio might reflect attenuated cytotoxicity of CD8 + T cells against tumors. This suggestion may account for the clinical implication that a high PD-1 + /CD8 + tumorinfiltrating lymphocyte ratio is a poor prognostic factor for pulmonary adenocarcinomas in this study.…”

Section: Discussionmentioning

confidence: 96%

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

et al. 2015

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Immunotherapies targeting the programmed cell death-1/programmed cell death-ligand 1 pathway have emerged as promising therapeutic strategies for lung cancer. However, the expression pattern and prognostic implications of programmed cell death-ligand 1 and 2 and programmed cell death-1 in comparison with the histology and genetic alterations in pulmonary adenocarcinomas remains unclear and thus were addressed here. Programmed cell death-ligand 1 and 2 expression in tumor cells and the quantities of programmed cell death-1 + and CD8 + tumor-infiltrating lymphocytes were immunohistochemically evaluated in 497 resected pulmonary adenocarcinomas and analyzed according to clinicopathological and genetic statuses. Programmed cell death-ligand 1 and 2 expression were observed in 59% and 64% of pulmonary adenocarcinomas, respectively, and showed a strong positive correlation with each other (Po 0.001). Programmed cell death-ligand 1 expression was higher in nodal metastasis cases (P = 0.006), smokers (P = 0.056), poorly differentiated tumors and histologic subtypes of solid and micropapillary patterns (Po0.001). There was no significant difference in programmed cell death-ligand 1 and 2 expression according to EGFR mutation status. However, programmed cell death-ligand 1 expression was correlated with ALK translocation (P = 0.054) and expression of EGFR and MET (Po 0.001). Meanwhile, programmed cell death-ligand 2 expression was correlated with ALK translocation (P = 0.052), and expression of MET (Po 0.001) and ERBB2 (P = 0.013). The numbers of CD8 + and programmed cell death-1 + lymphocytes were higher in smokers (P = 0.012 and 0.016) and MET-expressing adenocarcinomas (Po 0.001). Patients expressing programmed cell death-ligand 1 and/or high ratios of programmed cell death-1 + /CD8 + lymphocytes showed shorter disease-free survival (P = 0.001). Our study demonstrated that programmed cell death-ligand 1 and 2 expression varied with histology, EGFR, ALK, MET, and ERBB2 statuses, and activation of the programmed cell death-1/programmed cell death-ligand 1 pathway may be a poor prognostic factor in pulmonary adenocarcinomas.

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“…demonstrated PD-1 to be an independent prognostic factor for both OS and disease-free survival in patients with MSS tumours. 17 Moreover, PD-1 expression has been demonstrated to carry an independent favourable impact in gastric, 47 ovarian, 48 and head and neck cancer, 49 among others. Further studies are warranted to elucidate the prognostic impact of PD-1 expression in CRC, particularly regarding PTL.…”

Section: Discussionmentioning

confidence: 99%

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

et al. 2018

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Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 has been demonstrated to confer a prognostic value in colorectal cancer (CRC), but no studies have investigated whether this association differs according to tumour location. In this study, immunohistochemical expression of PD-1 and PD-L1 was analysed in tissue microarrays with primary tumours from 557 incident CRC cases from a prospective population-based cohort. Univariable and multivariable Cox regression analyses, adjusted for age, sex, TNM stage, differentiation grade and vascular invasion, were applied to determine the impact of biomarker expression on 5-year overall survival (OS), in the entire cohort and in subgroup analysis of right colon, left colon, and rectum. High PD-L1 expression on tumour-infiltrating immune cells was an independent factor of a prolonged OS in the entire cohort (hazard ratio [HR] = 0.49; 95% confidence interval [CI] CI 0.35 – 0.68), and in tumours of the right colon (HR = 0.43; 95% CI 0.25 – 0.74) and the left colon (HR = 0.28; 95% CI 0.13 – 0.61), but not in rectal cancer. Tumour-specific PD-L1-expression was not prognostic, neither in the full cohort nor according to tumour location. High immune cell-specific PD-1 expression was associated with a prolonged OS in the entire cohort and in tumours of the right colon, but not in the left colon or rectum, and only in univariable analysis. In conclusion, these results demonstrate that immune cell-specific PD-L1 and PD-1 expression is prognostic in a site-dependent manner, whereas tumour-specific PD-L1-expression is not prognostic in CRC.

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PD-1–Expressing Tumor-Infiltrating T Cells Are a Favorable Prognostic Biomarker in HPV-Associated Head and Neck Cancer

Cited by 557 publications

References 52 publications

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer

Clinicopathologic analysis of programmed cell death-1 and programmed cell death-ligand 1 and 2 expressions in pulmonary adenocarcinoma: comparison with histology and driver oncogenic alteration status

Expression of programmed cell death protein 1 (PD-1) and its ligand PD-L1 in colorectal cancer: Relationship with sidedness and prognosis

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