Inflammatory cell infiltration of tumors: Jekyll or Hyde

Abstract

Inflammatory cell infiltration of tumors contributes either positively or negatively to tumor invasion, growth, metastasis, and patient outcomes, creating a Dr. Jekyll or Mr. Hyde conundrum when examining mechanisms of action. This is due to tumor heterogeneity and the diversity of the inflammatory cell phenotypes that infiltrate primary and metastatic lesions. Tumor infiltration by macrophages is generally associated with neoangiogenesis and negative outcomes, whereas dendritic cell (DC) infiltration is typically associated with a positive clinical outcome in association with their ability to present tumor antigens (Ags) and induce Ag-specific T cell responses. Myeloid-derived suppressor cells (MDSCs) also infiltrate tumors, inhibiting immune responses and facilitating tumor growth and metastasis. In contrast, T cell infiltration of tumors provides a positive prognostic surrogate, although subset analyses suggest that not all infiltrating T cells predict a positive outcome. In general, infiltration by CD8(+) T cells predicts a positive outcome, while CD4(+) cells predict a negative outcome. Therefore, the analysis of cellular phenotypes and potentially spatial distribution of infiltrating cells are critical for an accurate assessment of outcome. Similarly, cellular infiltration of metastatic foci is also a critical parameter for inducing therapeutic responses, as well as establishing tumor dormancy. Current strategies for cellular, gene, and molecular therapies are focused on the manipulation of infiltrating cellular populations. Within this review, we discuss the role of tumor infiltrating, myeloid-monocytic cells, and T lymphocytes, as well as their potential for tumor control, immunosuppression, and facilitation of metastasis.

Microenvironmental regulation of metastasis

“…For example, infiltration of CD8 + T cells and mature dendritic cells is associated with a favourable prognosis in colorectal cancer and head and neck cancer (reviewed in REF. 31). An extensive macrophage infiltration, however, correlates with poor patient prognosis in >80% of cancers analysed, including breast, thyroid and bladder cancer in which there is a positive association with metastasis (reviewed in REFS 31,32).…”

Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouse

“…These cells were suspended in RPMI 1640 medium (Invitrogen, Carlsbad, CA) including 100 μg/ml streptomycin and 100 U/ml penicillin. Purified CD11b + GR-1 + cells were first treated with mitomycin C (Nacalai tesque Inc, Kyoto) at 10 μg/mL for 2 hours at 37°C in 5% CO 2 …”

“…These cells have been reported to express CD11b and GR-1 in mouse models (1)(2)(3)(4). In tumor microenvironment, MDSCs inhibit T cell activation via arginase (ARG)-1 and nitric oxidase activation, resulting in tumor growth (4).…”

CEA/CD3 bispecific antibody MEDI-565/AMG 211 activation of T cells and subsequent killing of human tumors is independent of mutations commonly found in colorectal adenocarcinomas

“…Tumor antigen-specific T cells are readily found within tumors and in tumor-draining lymph nodes, but the clearance of established tumors by the immune system is rare. 32 Multiple mechanisms exist to subvert antigen-specific, T cell-mediated destruction of tumor cells thereby resulting in tumor immune evasion. 33 These include down-regulation of major histocompatibility (MHC) class I complexes on the surface of tumor cells, lack of tumor antigen processing and presentation, escape from T-cell induced destruction, as well as induction of T cell anergy, exhaustion, or apoptosis, and suppression of effector T cell function by coinhibitory receptor pathway signaling or suppressor cell populations, in particular by regulatory T cells.…”