Pathology, research and practice · 2023
TAMs PD-L1(+) in the reprogramming of germ cell tumors of the testis.
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Melotti Sofia, Ambrosi Francesca, Franceschini Tania, Giunchi Francesca, Filippo Giorgia Di, Franchini Eugenia, Massari Francesco, Mollica Veronica, Tateo Valentina, Bianchi Federico Mineo, Colecchia Maurizio, Acosta Andres Martin, Lobo João, Fiorentino Michelangelo, Ricci Costantino
Аннотация
BACKGROUND: In recent years, several studies focused on the process of reprogramming of seminoma (S) cells, which regulates the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (GCTT) and finally to embryonal carcinoma (EC) and other nonseminomatous GCTT (NS-GCTT). The accepted pathogenetic model is driven and regulated by cells (macrophages, B- and T-lymphocytes) and molecules of the tumor microenvironment (TME). Herein, we tested a series of GCTT with double staining (DS) for CD68-PD-L1 to evaluate tumor-associated macrophages (TAMs) expressing programmed death-ligand 1 (PD-L1) [TAMs PD-L1(+)] and clarify if these cells may be involved in establishing the fate of GCTT.
METHODS: We collected 45 GCTT (comprising a total of 62 different components of GCTT). TAMs PD-L1(+) were evaluated with three different scoring systems [TAMs PD-L1(+)/mm2, TAMs PD-L1(+)/mm2H-score, TAMs PD-L1(+) %], and compared using pertinent statistic tests (Student's t-test and Mann-Whitney U test).
RESULTS: We found that TAMs PD-L1(+) values were higher in S rather than EC (p = 0.001, p = 0.015, p = 0.022) and NS-GCTT (p < 0.001). P-S showed statistically significant differences in TAMs PD-L1(+) values compared to S-C (p < 0.001, p = 0.006, p = 0.015), but there were no differences between S-C and EC (p = 0.107, p = 0.408, p = 0.800). Finally, we found statistically significant differences also in TAMs PD-L1(+) values between EC and other NS-GCTT (p < 0.001).
CONCLUSIONS: TAMs PD-L1(+) levels gradually decrease during the reprogramming of S cells {P-S [(high values of TAMs PD-L1(+)] → S-C and EC [(intermediate values of TAMs PD-L1(+)] → other NS-GCTT [(low values of TAMs PD-L1(+)], supporting a complex pathogenetic model where the interactions between tumor cells and TME components [and specifically TAMs PD-L1(+)] play a key role in determining the fate of GCTT.
METHODS: We collected 45 GCTT (comprising a total of 62 different components of GCTT). TAMs PD-L1(+) were evaluated with three different scoring systems [TAMs PD-L1(+)/mm2, TAMs PD-L1(+)/mm2H-score, TAMs PD-L1(+) %], and compared using pertinent statistic tests (Student's t-test and Mann-Whitney U test).
RESULTS: We found that TAMs PD-L1(+) values were higher in S rather than EC (p = 0.001, p = 0.015, p = 0.022) and NS-GCTT (p < 0.001). P-S showed statistically significant differences in TAMs PD-L1(+) values compared to S-C (p < 0.001, p = 0.006, p = 0.015), but there were no differences between S-C and EC (p = 0.107, p = 0.408, p = 0.800). Finally, we found statistically significant differences also in TAMs PD-L1(+) values between EC and other NS-GCTT (p < 0.001).
CONCLUSIONS: TAMs PD-L1(+) levels gradually decrease during the reprogramming of S cells {P-S [(high values of TAMs PD-L1(+)] → S-C and EC [(intermediate values of TAMs PD-L1(+)] → other NS-GCTT [(low values of TAMs PD-L1(+)], supporting a complex pathogenetic model where the interactions between tumor cells and TME components [and specifically TAMs PD-L1(+)] play a key role in determining the fate of GCTT.