Low numbers of M2 macrophages in tumour microenvironment associated with superior response to immunotherapy in Hodgkin lymphoma

A low baseline number of M2 macrophages in Hodgkin lymphoma patients treated with nivolumab was associated with complete remission and high progression-free survival (PFS), Russian investigators showed.

One of the explanations for the depressed anti-tumour response in classical Hodgkin lymphoma is hyperexpression of inhibitory immune checkpoint receptors on T cells as well as increased proportion of M2 macrophages in the tumour microenvironment. The presence of high number of M2 has been demonstrated to worsen the prognosis of patients treated with standard chemotherapy, while data regarding the prognostic value of tumour microenvironment features in patients treated with PD-1 inhibitors is limited.

A retrospective study included 61 primary tumour samples from patients with relapsed/refractory Hodgkin lymphoma treated with nivolumab, and 15 repeated samples were obtained during relapse or progression of disease after immunotherapy [1]. The tumour microenvironment was characterised by the proportion of cells positive for CD68, CD163, PD-1, LAG-3, TIM-3, CTLA-4, TIGIT, c-MAF present in the samples. The antibody combination CD163/c-MAF was used for identification of M2, the anti-inflammatory-like macrophages. Dr Liudmila Fedorova (Pavlov University, Russia) presented the results [1].

Both a relatively low presence of CD163-positive cells (P=0.0086) and CD68-positive cells (P=0.037) at baseline appeared to be associated with an inferior 4-year PFS after treatment with nivolumab, whereas a relatively low presence of CD163/c-MAF-positive (i.e. M2) cells was associated with a superior 4-year PFS (P=0.014; see Figure). In addition, an association was observed between complete remission achievement to nivolumab and a lower level of M2 in primary biopsies (P=0.047). In the analysis of sequential samples, an increase of PD-1-positive and LAG-3-positive T cells and depletion of CD68-positive and CD163-positive cells was observed after nivolumab treatment.

Figure: Presence of tumour-associated macrophages predicts PFS outcome of nivolumab treatment [1]



“We found that low numbers of M2 macrophages in primary samples were associated with achievement of complete response and higher PFS,” concluded Dr Fedorova.

1. Fedorova L, et al. Immune microenvironment in classical Hodgkin lymphoma: Composition and dynamics in patients with relapsed/refractory disease. Abstract 832MO, ESMO Congress 2021, 16–21 September.

 

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Posted on 19 November, 202115 February, 2024