Reshaping Antitumor Immunity with Chemo‐Photothermal Integrated Nanoplatform to Augment Checkpoint Blockade‐Based Cancer Therapy

Abstract

Immune checkpoint therapy promotes cytotoxic T lymphocytes (CTLs) activity to eliminate tumors. Nevertheless, their effectiveness in solid tumors is limited by inadequate infiltration of CTLs and suppressive tumor microenvironment (TME). Herein, an anti‐PD‐1 antibody coupled chemo‐photothermal integrated nanoplatform (A/Au@MSMs‐P) is proposed to reshape antitumor immunity against cancer. The matrix metalloproteinase‐2 (MMP‐2) responsive A/Au@MSMs‐P promotes the separation of abemaciclib‐loaded gold‐silica nanoparticles (A/Au@MSMs) and anti‐PD‐1 antibody, achieving a triple‐coordinated strategy to enhance checkpoint blockade therapy. First, chemo‐photothermal therapy of A/Au@MSMs induces cell cycle arrest in G1 phase and promotes tumor cells apoptosis to achieve local ablation. Second, immunogenic death of tumor cells promotes the maturation of dendritic cells and recruits antigen‐specific CTLs into tumor tissue to promote immune activation. Third, abemaciclib markedly suppresses the proliferation of regulatory T cells (Tregs) to alleviate the immunosuppression of the TME and potentiates the effectiveness of CTLs. This triple‐coordinated strategy not only reshapes the antitumor immunity to enhance checkpoint blockade, but also cooperates with chemo‐photothermal therapy, leading to improved antitumor efficiency and prolonged survival rate. Taken together, this study presents a promising strategy for improving checkpoint therapy response and has great potential in future cancer therapy.

Photothermal-Chemotherapy Enhancing Tumor Immunotherapy by Multifunctional Metal–Organic Framework Based Drug Delivery System

“…Damage-associated molecular patterns (DAMPs), such as secreted adenosine triphosphate (ATP), exposed calreticulin (CRT), and released high mobility group protein B1 (HMGB1), have mediated the immunogenic characteristics of ICD . Combining two therapeutic approaches such as photothermal therapy (PTT) and chemotherapy may stimulate the intrinsic functioning of the immune response by inducing higher levels of ICD for increasing tumor immunogenicity. , Therefore, it will be a good choice for clinically chemotherapeutic drugs of photothermal effect . Mitoxantrone (MTO) exhibits a strong absorption at 600–700 nm and could induce ICD of tumor cells, enhancing tumor immunogenicity and improving the prognosis of metastatic tumors. , However, MTO can also cause a series of undesirable adverse effects.…”

Two‐Wave Variable Nanotheranostic Agents for Dual‐Mode Imaging‐Guided Photo‐Induced Triple‐Therapy for Cancer

“…ii) Local heating promotes the release of Abemaciclib, which induces G1 cycle arrest in tumor cells by inhibiting the phosphorylation of retinoblastoma. [17] Abemaciclib could also effectively reduce the proportion of Tregs and secretion of IL-10 and TGF-𝛽 in tumor tissues, thus alleviating the immunosuppressive tumor microenvironment. [18] iii) DCs are the most effective antigenpresenting cells, which can uptake, process, and present antigens to trigger an effective antitumor T cell response.…”

Remodelling of the tumour-lymph node immune microenvironment promotes T- and NK-cell comobilization for tumour immunotherapy

“…The tumour microenvironment interacts with surrounding immune cells via the circulatory and lymphatic systems, which signi cantly affects the antitumour immune response and clinical e cacy 3,4 . Remodelling the immunosuppressive tumour microenvironment has been widely used to enhance immunotherapy [5][6][7] ; however, the effects of immunotherapy still need improvement. Lymph node (LN) is the meeting grounds for dendritic cell (DC) antigen presentation and effective cytotoxic T lymphocyte (CTL) activation, showing strategic signi cance in tumour immunotherapy 8,9 .…”