Role of immune escape mechanisms in Hodgkin's lymphoma development and progression: a whole new world with therapeutic implications

Abstract

Hodgkin's lymphoma represents one of the most frequent lymphoproliferative syndromes, especially in young population. Although HL is considered one of the most curable tumors, a sizeable fraction of patients recur after successful upfront treatment or, less commonly, are primarily resistant. This work tries to summarize the data on clinical, histological, pathological, and biological factors in HL, with special emphasis on the improvement of prognosis and their impact on therapeutical strategies. The recent advances in our understanding of HL biology and immunology show that infiltrated immune cells and cytokines in the tumoral microenvironment may play different functions that seem tightly related with clinical outcomes. Strategies aimed at interfering with the crosstalk between tumoral Reed-Sternberg cells and their cellular partners have been taken into account in the development of new immunotherapies that target different cell components of HL microenvironment. This new knowledge will probably translate into a change in the antineoplastic treatments in HL in the next future and hopefully will increase the curability rates of this disease.

Figure 1

Immunohistochemical staining of inflammatory background in HL: T lymphocytes (CD4 and CD8), NK cells (CD57), and cytotoxic cells (TIA-1).

Figure 2

Reed-Sternberg cell (a) seen in a cellular background rich in lymphocytes of a classical Hodgkin's lymphoma. Immunohistochemical expression of the activation markers CD30 (b) and CD15 (c).

Figure 3

Immunohistochemical staining of immunosuppressive cells in HL: tumor-associated macrophages TAM (STAT-1 and CD68) and regulatory T cells (FOXP3 and LAG-3).

Figure 4

Representation of the two immune patterns observed in HL significantly associated with their clinicopathological features. The immunosurveillance pattern with a high proportion of infiltrating T lymphocytes, NK cells, DCs, activated CTL, but low proportion of resting CTL and TAM is associated with a favorable outcome. The immune escape pattern with a high proportion of infiltrating resting CTL and TAM, but low proportion of T lymphocytes, NK cells, DCs, and activated CTL is associated with an unfavorable outcome. MC, mixed cellularity; NS, nodular sclerosis; CR, complete response.

Figure 5

Therapeutic strategies to overcome immune escape in HL. AcMo: monoclonal antibodies. H/RS cells: Hodgkin's/Reed-Sternberg cells. CTL: cytotoxic T lymphocytes. HMGB1: high-mobility group protein B1. TLR4: Toll-like receptor 4.