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Immune surveillance is a mechanism by which the immune system identifies cancer cells and eliminates them via cytotoxic T-cells (CTLs). Tumors have developed strategies to escape immune surveillance including an altered expression of various immune checkpoints leading to the suppression of CTL function.^{^} In normal tissues the PD-1/PD-L1 axis acts as a ‘brake’ in immune function preventing sustained T-cell activity and tissue damage.^% T-cells are activated via binding of the TCR to the MHC/antigen complex on an APC or tumor cell.^` Upon T-cell activation, PD-1 expression is induced.^s A tumor cell can upregulate PD-L1 expression to mimic normal cells and “turn off” T-cells to escape immune surveillance.^+*o

Blocking the PD-1/PD-L1 signaling pathway by an anti-PD-1 antibody allows T-cells to maintain their effector functions.^\ The Fc portion of the anti-PD-1 antibody and its limited interaction with FcγR are important for its therapeutic activities.ⁱ Activated tumor-specific T-cells mediate the destruction of tumor cells and secrete cytokines that activate and recruit other immune cells to participate in the antitumor response.^R Anti-PD-1 antibodies, which bind to FcγRs, likely mediate the crosslinking between PD-1+ T cells and FcγR+ macrophages. Such crosslinking could potentially induce macrophages to phagocytize PD-1+ T cells and possibly diminish antitumor responses.ⁱ

Tislelizumab is a humanized IgG4 mAb with high affinity and binding specificity against PD-1.^& Tislelizumab was specifically engineered to minimize binding to FcγR on macrophages.ⁱ Minimal binding of anti-PD-1 antibodies to FcγR abrogates antibody-dependent cellular phagocytosis, a potential mechanism of T-cell clearance.^8Mc88 Binding surface of tislelizumab on PD-1 overlapped largely with that of PD-L1, leading to the complete blockade of PD-1/PD-L1 interaction (>99%).^8w

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For an exhaustive list of tislelizumab monotherapy and combination clinical trials view the IL[L6J1kL(0 DWu9Wbi.

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1. Zhang T et al. The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions. OvA{lE =||wuO@ 9\\?^0a%q4. 2018;67:1079–1090.
2. Lu, S. et al. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. ,. Y+nBVd. jRIgc. Off. Publ. Int. Assoc. Study Lung Cancer 2021;16:1512–1522.
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9. Desai J et al. Preliminary results from subsets of patients (pts) with advanced gastric cancer (GC) and esophageal carcinoma (EC) in a dose-escalation/expansion study of BGB-A317, an anti-PD-1 monoclonal antibody (mAb). YFF c(L0i 2017; 28(suppl_5):v122–v141.
10. Arlauckas SP et al. In vivo imaging reveals a tumor-associated macrophage–mediated resistance pathway in anti–PD-1 therapy. [PG =SZN[: K-9 2017; 9:eaal3604.
11. Dahan R et al. FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. At?4H1 ~}TT 2015; 28:285–295.
12. Hong Y et al. Tislelizumab uniquely binds to the CC0loop of PD-1 with slow-dissociated rate and complete PD-L1 blockage. Iq^? LgoG etV 2021; 11(3):782-792