Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma

Abstract

Diffuse malignant mesothelioma of the pleura is a highly aggressive tumor typically associated with short survival. ALCAM (CD166), a type I transmembrane protein, is a member of the immunoglobulin superfamily. In normal cells, ALCAM regulates physiological processes such as angiogenesis and immune response. In cancer, it is associated with neoplastic progression, including invasion, migration, and metastasis. Furthermore, ALCAM is considered one of the cancer stem cell markers such as ALDH1 (ALDH1A1) and SALL4. The PD-L1 (CD274)/PD-1 (PDCD1, CD279) pathway is crucial for the modulation of immune responses in normal cells. Nevertheless, pathologic activation of the PD-L1/PD-1 pathway participates in immune evasion by tumor cells. Many PD-L1-expressing tumor cells have been identified in different types of cancer, including malignant mesothelioma. In this study, 175 well-characterized primary diffuse pleural mesotheliomas, including the epithelioid (n = 148), biphasic (n = 15), and sarcomatoid (n = 12) histotypes, were evaluated immunohistochemically for cancer stem cell markers (ALCAM, ALDH1, and SALL4) and PD-L1 expression. Twenty-five percent of the mesotheliomas (43/175) expressed ALCAM, whereas ALDH1 and SALL4 positivity was seen in 1% to 2% of cases. Thirty-three percent of the analyzed tumors (57/175) contained PD-L1-positive cells. Overall survival was significantly decreased in the cohort of patients with ALCAM- or PD-L1-positive tumors (both P < .01). Furthermore, the multivariate Cox hazards regression analysis identified ALCAM and PD-L1 (both P < 0.01) as potential independent risk factors. Thus, a combination of these 2 markers might be useful for prognostication and planning the treatment of patients with malignant pleural mesothelioma.

Association of PD-L1 Expression with Prognosis Among Patients with Ten Uncommon Advanced Cancers

“…Results from the current retrospective longitudinal study suggest that PD-L1 expression is associated with shorter OS after first-line SOC therapy (nonimmunotherapy) across a range of tumors (unadjusted HR: 1.39 [95% CI: 1.07–1.81]; p = 0.0136). Consistent with our findings, previous studies have identified an association of PD-L1 expression with shorter OS in patients with malignant salivary gland tumor [ 31 ], malignant pleural mesothelioma [ 32 ], NSCLC [ 30 , 33 ] and pancreatic cancer [ 30 , 34 ]. In contrast, other studies have reported that PD-L1 expression was associated with longer OS in patients with NSCLC [ 35 ] and SCLC [ 36 ].…”

Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma

“…The composition of TME holds therapeutic and prognostic implications [ 6 , 7 ]. Stage and histology are currently accepted prognostic indicators [ 5 ], but evidence is accumulation that infiltrating immune cells and expression of immune checkpoints are of high prognostic value in MPM [ 7 , 50 , 51 , 52 , 53 ]. Infiltration of M2 macrophages seems to be associated with worse prognoses [ 18 , 19 , 20 ], as is PD-L1 expression [ 50 , 51 , 52 , 53 ].…”

“…Stage and histology are currently accepted prognostic indicators [ 5 ], but evidence is accumulation that infiltrating immune cells and expression of immune checkpoints are of high prognostic value in MPM [ 7 , 50 , 51 , 52 , 53 ]. Infiltration of M2 macrophages seems to be associated with worse prognoses [ 18 , 19 , 20 ], as is PD-L1 expression [ 50 , 51 , 52 , 53 ]. Infiltration of cytotoxic T cells was associated with better prognosis in MPM in most studies [ 21 , 33 , 36 , 37 , 38 ].…”

“…PD-L1 expression is higher in non-epithelioid mesothelioma compared to epithelioid mesothelioma (37.5–97.4% vs. 6.7–31%) [ 21 , 25 , 42 , 50 , 51 , 52 , 53 , 54 ]. Several studies found higher PD-L1 expression to be an independent prognostic indicator for worse overall survival in multivariate data analysis [ 50 , 52 , 53 , 55 ]. Khanna et al [ 54 ] analyzed PD-L1 expression in peritoneal and pleural fluid of respectively six and three mesothelioma patients.…”

<p>In silico Analysis, Molecular Docking, Molecular Dynamic, Cloning, Expression and Purification of Chimeric Protein in Colorectal Cancer Treatment</p>

“…This molecule is a vital factor not only for cell survival, motility, and cell growth but also for invasion during tumor progression and metastases. 7,8 CD166 is a glycoprotein that was initially discovered as an MHC-I for the cell surface receptor of T lymphocyte (CD6). 9 It contributes to 1) heterotypic adhesion to the lymphocyte cell-surface receptor (CD6) 10 and 2) homotypic adhesion.…”