Dynamic CD8+ T Cell Cooperation with Macrophages and Monocytes for Successful Cancer Immunotherapy

Abstract

The essential roles endorsed by macrophages and monocytes are well established in response to infections, where they contribute to launching the differentiation of specific T-lymphocytes for long-term protection. This knowledge is the result of dynamic studies that can inspire the cancer field, particularly now that cancer immunotherapies elicit some tumor regression. Indeed, immune responses to cancer have mainly been studied after tumors have escaped immune attacks. In particular, the suppressive functions of macrophages were revealed in this context, introducing an obvious bias across the literature. In this review, we will focus on the ways inwhich monocytes and macrophages cooperate with T-lymphocytes, leading to successful immune responses. We will bring together the preclinical studies that have revealed the existence of such positive cooperation in the cancer field, and we will place particular emphasis on proposing the underlying mechanisms. Finally, we will give some perspectives to decipher the functional roles of such T-cell and myeloid cell interactions in the frame of human cancer immunotherapy.

Spatial Phenotyping of Nodular Lymphocyte Predominant Hodgkin Lymphoma and T-cell/Histiocyte-Rich Large B-cell Lymphoma

“…This nding may have therapeutic implications given that monocyte/cytotoxic T-cell interactions have been shown to in uence responses to immune therapy and prognosis. [50] A signi cantly higher number of immature monocytes detected in THRLBCL in our cohort, raises the possible acquisition of a tolerogenic TME, which has been shown to correlate with suppression of T-cell proliferation, immune evasion, and tumor dissemination. [17,48,51] The molecular signature of THRLBCL shows upregulation of interferon-dependent pathway genes which promote immune tolerance in lymphoma.…”

“…In addition, monocytes in THRLBCL interacted strongly with both TFH and cytotoxic T-cells, which may in uence response to therapeutic approaches targeting immune checkpoints as shown in other lymphomas with an in amed TME. [50,55] Nodular NLPHL patterns had increased TME B-cells and TH cells but decreased activated TFH cells compared to NLPHL pattern E and THRLBCL. A strong interaction between TH cells and cytotoxic T-cells was seen in the nodular groups, whereas the interaction between TH cells and tumor cells was more pronounced in diffuse cases.…”

Mathematically mapping the network of cells in the tumor microenvironment

“…Moreover, we also saw increased activity of the S100 calcium-binding protein A8 and A9 (S100A8/-A9), which is a biomarker of tumor progression also in response to ICB therapy in melanoma patients, in agreement with their appearance in non-responders 52 . Additionally, non-responders showed higher expression of major histocompatibility complex class I-B (HLA-B) binding to CD8(A and B) T cell receptors, which is linked to downregulation of CD8+ T-cell activity 53 and T-cell exhaustion 54 mediated by pro-tumor macrophages. Interestingly, major histocompatibility complex class II (HLA-DM, -DP, -DQ, -DR) interaction with cluster for differentiation 4 (CD4), which is normally related to antigen presentation, is also slightly higher in non-responders.…”

Targeting Wnt/β-catenin signaling using XAV939 nanoparticles in tumor microenvironment-conditioned macrophages promote immunogenicity

“…Although the role of Wnt/β-catenin signaling in Ag presentation by DCs and activation of effector T cell responses during tumor progression is well defined [ 83 ], the role of β-catenin activation in TAMs and effect on T cell responses is poorly understood. Moreover, the macrophages can perform cross-Ag presentation to CD8 + T cells [ 106 ]. Accordingly, our in vitr o data demonstrate that β-catenin inhibition in MC-macrophage co-culture promotes naïve CD8 + T cell proliferation.…”