<scp>PD</scp>‐L1 expression and survival among melanoma patients treated with standard immunotherapy or chemotherapy

Steiniche, Torben; Danielsen, Allan Vestergaard; Wang, Z.; Feng, Yu; Nielsen, Patricia Switten; Bastholt, Lars; Svane, Inge Marie; Dolled‐Filhart, Marisa; Emancipator, Kenneth; Weiner, Russell; Busch-Sørensen, M.; Zhou, Wei

doi:10.1111/jdv.14106

Cited by 4 publications

(3 citation statements)

References 13 publications

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“…We did not find any significant association between PD‐L1 expression on tumour cells of primary melanoma and OS, as previously shown . In melanoma, the prognostic significance of PD‐L1 expression remains controversial, being associated with either a poor or a better prognosis …”

Section: Discussionsupporting

confidence: 79%

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Bence

Hofman

Chamorey

et al. 2019

Acad Dermatol Venereol

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Background Recent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD-L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas.Objectives We investigated whether the presence and the features of pretreatment CD8 + tumour-infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma.Methods In this retrospective study, we evaluated the association of PD-L1 expression ≥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non-ICIs).Results PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (j = 0.283). No significant association was noted between PD-L1 expression and CD8 + TIL profile analysed as single markers and OS or response to immunotherapy.Instead, their combined analysis in primary melanoma samples showed that the PD-L1À/CD8 + status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non-ICIs (P = 0.009). Conversely, the PD-L1+/CD8 + status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non-ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8 + TIL+/PD-L1À (P = 0.02). ConclusionsThe pretreatment combination of PD-L1 expression with the level of CD8 + TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens. JEADV Funding sourceThis work did not receive any financial specific support.

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Section: Discussionsupporting

confidence: 79%

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Bence

Hofman

Chamorey

et al. 2019

Acad Dermatol Venereol

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“…Several studies have reported that high PD-L1 expression influences the OS of cancer patients ( Aguiar et al, 2017 ; Steiniche et al, 2017 ; Svensson et al, 2019 ). For example, high PD-L1 expression was associated with a prolonged OS in gastric cancer, whereas high PD-L1 expression in oesophagal cancer was associated with a shorter OS ( Svensson et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue

Sommer

Ebersbach²,

Beier³

et al. 2022

Front. Mol. Biosci.

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Immune checkpoint inhibitors have become a promising new therapy for cancer treatment. However, due to prostate cancer’s high heterogeneity and immune-suppressive tumour microenvironment, clinical trials with immune checkpoint inhibitors for prostate cancer resulted in low or no response. This descriptive and retrospective study investigates the influence of androgen deprivation therapy (ADT) on PD-L1 expression and CD8+ T-cell tumour infiltration and activity in primary prostate cancer tissue. Therefore, immunohistochemistry was used to assess PD-L1, CD8+ T-cell, and the immune activation marker Granzyme B (GrB) in PCa tissue before and under ADT. In line with previous studies, few prostate cancer tissues showed PD-L1 expression and CD8+ T-cell infiltration. However, PD-L1 expression levels on tumour cells or infiltrating immune cells above 5% generated an immune-suppressive tumour microenvironment harbouring hypofunctional CD8+ T-cells. Moreover, analysis of a longitudinal patient cohort before and under ADT revealed that ADT increased hypofunctional CD8+ T cells in the tumour area suggesting a tumour immune milieu optimal for targeting with immunotherapy.

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“…In cutaneous melanoma, the relationship between PD-L1 staining and prognosis observed across studies is still inconsistent [29][30][31][46][47][48]. However, several studies have reported similar association between PD-L1 expression and a poor prognosis in cutaneous melanoma [31,47,49,50] and other solid tumours [47].…”

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome

Lassalle

Nahon-Estève

Frouin

et al. 2020

IJMS

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Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

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PD‐L1 expression and survival among melanoma patients treated with standard immunotherapy or chemotherapy

Cited by 4 publications

References 13 publications

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Association of combined PD‐L1 expression and tumour‐infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma

Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue

PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome

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