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

Abstract

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.

Overexpressed Pseudogene HLA-DPB2 Promotes Tumor Immune Infiltrates by Regulating HLA-DPB1 and Indicates a Better Prognosis in Breast Cancer

“…Also, the continuous anti-tumor effect of ICIs not only requires sufficient lymphocytes infiltrating in the tumor microenvironment but also depends on the high immune checkpoint expression levels of tumor cells ( 5 , 13 ). Hence, we also analyzed the relationship between HLA-DPB2/HLA-DPB1 expression and immune checkpoints.…”

“…TILs are predictive markers of the tumor-immune microenvironment and the response to ICIs therapy ( 11 ). Emerging studies have shown that the greater number of TILs, the stronger response to ICIs therapy ( 12 , 13 ). The future of immunotherapy in BC lies in the combination of ICIs with strategies that activate the immune system to pursue maximal antitumor efficacy ( 14 ).…”

Double primary malignant melanoma on the forearm and the chest with detection of common axillary sentinel lymph nodes

“…In cases of multiple primary melanoma with metastases, the primary lesion should be clarified because the effect of immune checkpoint inhibitors depends on its characteristics. 5 However, if the SLN from different primary lesions are the same, as in our case, and the SLN are metastatic, the primary lesions of the metastases cannot be detected by routine examination. Therefore, in such cases, genetic analyses of LN metastases and each primary lesion should be considered to determine which primary lesion metastasized to the SLN.…”

Molecular and Immune Biomarkers for Cutaneous Melanoma: Current Status and Future Prospects

“…On the other hand, the prognostic value of the PD-L1 expression in patients with metastatic melanoma remains even more controversial, having been associated with better or worst prognosis in different studies [79][80][81][82][83]. Indeed, the results of 2 different studies in the adjuvant setting, one comparing nivolumab to ipilimumab and pembrolizumab to placebo, respectively, showed that recurrence-free survival was longer in patients with PD-L1 positive tumors, irrespectively from the treatment [4,84].…”