Role of tumor-infiltrating immune cells and HLA expression in influencing tumor progression and the effectiveness of anticancer treatment
Hegyi Barbara
Pathological and Oncological Divison
Dr. Matolcsy András
Országos Onkológiai Intézet, Tanácsterem
2026-04-20 14:00:00
Molekuláris és experimentális onkológia
Dr. Bödör Csaba
Ladányi Andrea
Dr. Balázs Margit
Dr. Nardainé Imrédi Eleonóra
Dr. Kulka Janina
Dr. Tőkés Anna Mária
Dr. Biró Krisztina
The introduction of ICI therapy has changed the treatment protocol for melanoma, providing
patients with a significant survival advantage compared to previous treatment options. Since only a
part of the patients benefit from the therapy, and the development of resistance mechanisms can also
be expected in them after a while, it has become necessary to develop biomarkers that can be
sufficiently predictive of ICI therapy and explain the background of the resistance that has developed.
In our studies, we focused on investigating local immunological parameters, i.e., tumor cell
HLA expression and immune cell infiltration, as potential resistance mechanisms to ipilimumab
therapy and as predictive biomarkers of the efficacy of PD-1 inhibitor treatment in metastatic
melanoma patients.
In our first study we examined 29 metastatic melanoma samples (18 pre-treatment, 11 posttreatment)
from six patients treated with ipilimumab. We used immunohistochemical staining to
determine HLA class I expression level and the intratumoral infiltration of CD8+ T lymphocytes and
NK cells. We revealed HLA-I downregulation mainly in the case of progressing lesions of
nonresponding patients; in contrast, minimal or no change was found in responding patients. The
infiltration level of CD8+ T lymphocytes and NK cells showed no consistent change between pre- and
post-treatment samples.
In our second study we analyzed samples of 112 skin, subcutaneous and lymph node melanoma
metastases from 40 patients treated with nivolumab or pembrolizumab. We determined with
immunohistochemistry the HLA class I and class II expression level. The proportion of patients
showing HLA-II expression in ≥3% of melanoma cells was higher compared to non-responders and
two anti-HLA-I antibodies (HC10 and EMR8-5) showed similar results. A combined score of HLA-I
and -II expression proved very effective in predicting treatment response.
Our future plans are to validate a prospective study with longitudinal sample analyses in a larger
patient cohorts treated with ICI therapy.
