IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity

Abstract

Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs).

Tumor-infiltrating lymphocytes (TILs) from patients with glioma

“…27 In concert with IL-21, IL-15 has been shown to overcome immunosuppressive effects on tumor-reactive T cells, in part by neutralizing negative effects of tumor-associated macrophages 28 and by increasing antitumor activity in CD8 C T cells. 29 IL-2, IL-15 and IL-21-expanded TILs from glioma lesions could be used for cellular therapy with the hope to achieve clinically relevant responses as it has been reported for patients with melanoma or other solid cancers.…”

Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy

“…20 Fluorescent images were acquired with Nikon Eclipse Ti Inverted Microscope. The absolute numbers of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells were counted using Nikon Instruments Software (NIS-Elements AR3.2).…”

“…20 Before injection into the animals, NKT cells were cultured with interleukin (IL) 2 (200 U/mL; National Institutes of Health) for 10 days without TCR or CAR stimulation to achieve resting phase. Tumor growth was assessed by weekly bioluminescent imaging (Small Animal Imaging Core Facility, Texas Children's Hospital).…”

“…16,20 Moreover, NKT cells colocalize with TAMs and can kill or inhibit these growth-promoting cells 21 in a CD1d-dependent manner. 22 Because adoptive transfer of NKT cells has now become clinically feasible because of the development of reagents allowing robust ex vivo expansion of these cells, 20,23 we have proposed that The online version of this article contains a data supplement.…”

Tumor-associated macrophages: implications in cancer immunotherapy

“…Additionally, tumor-induced inflammation and hypoxia increase TAM-dependent production of CCL20 via activation of the NF-κB signaling pathway. CCL20, in turn, promotes the migration of Vα24-invariant NKT cells to the hypoxic tumor regions, where NK T-cell viability and antitumor function were suppressed [63]. Collectively, these evidences suggested that TAMs are a major force in disrupting antitumoral responses by effector cells in the TME and remain a significant obstacle to effective immunotherapy.…”