Figure 2. Targeting the RCC Immune Microenvironment.

(a) Stimulatory (text label in green) and inhibitory (text label in red) immune checkpoints on T cells that can be targeted by agonist and antagonist antibodies, respectively. (b) Novel cytokine therapies can activate T cell responses and stimulate the anti-tumor immune response. NHS-IL12 includes the NHS76 antibody that binds to necrotic debris and therefore directs IL-12 to tumors, where necrosis is prevalent. (c) The tryptophan–kynurenine–aryl hydrocarbon receptor and CD39–CD73–adenosine 2A receptor are immune metabolic pathways that can be targeted at multiple levels.

Ab: Antibody; TCR: T cell receptor; HLA: Human leukocyte antigen; PSGL-1: P-selectin glycoprotein ligand-1; VISTA: V-domain Ig suppressor of T cell activation; HHLA2: Human Endogenous Retrovirus-H Long Terminal Repeat-Associating Protein 2; CTLA-4: cytotoxic T-lymphocyte-associated protein 4; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; LAG-3: Lymphocyte activation gene-3; TIM-3: T cell immunoglobulin and mucin-domain containing-3; TIGIT: T cell immunoglobulin and ITIM domain; IL12-R: Interleukin 12 receptor; IL2-R: Interleukin 2 receptor; ATP: Adenosine triphosphate; AMP: Adenosine monophosphate; A2AR: adenosine 2A receptor; AhR: Aryl hydrocarbon receptor; Tryp: Tryptophan; Kyn: Kynurenine; RCC: Renal Cell Carcinoma; TDO: Tryptophan 2,3-dioxygenase; IDO1: Indoleamine 2,3-dioxygenase 1.

NOTE: Permission for reproduction of this figure was not granted by the publisher. For Figure 2, please refer to Figure 2 in the manuscript by Braun et al.:

Braun DA, Bakouny Z, Hirsch L, Flippot R, Van Allen EM, Wu CJ, Choueiri TK. Beyond conventional immune-checkpoint inhibition - novel immunotherapies for renal cell carcinoma. Nat Rev Clin Oncol. 2021 04; 18(4):199–214.