Oncolytic vaccinia virus acts synergistically with anti-PD-L1 antibody to enhance the killing of colon cancer cells by CD8+ T cells

Colon cancer (CC) is the most common type of colorectal cancer (CRC) that is the 2nd leading cancer diagnosed globally [1], [2] and has increasing incidence and mortality [3]. Despite great progress in diagnosis and treatment, many patients may develop metastases [4]. Therefore, investigating the regulatory mechanisms controlling cancer cell growth and metastasis and identifying more effective treatment options for patients suffering from metastatic CC can significantly improve the diagnosis, prevention, and treatment of CC.

Immunotherapies, enhancing the host immune response against malignant disease, have demonstrated efficacious treatment outcomes for multiple tumor types [5]. The colorectal tumors are immune responsive, and many patients at advanced stages benefit from immunotherapies over a long period [6]. PD-L1, also known as B7-H1 and CD274, is a crucial immunomodulatory molecule to inhibit immune response in physiological and pathological pathways via interaction with its receptor, PD-1 [7]. Anti-PD-L1 antibody has a key role in the immunomodulatory agents as it might act against signaling pathways that participate in adaptive immune suppression and therefore result in immune checkpoint blockade [8], [9]. Anti-mouse PD-L1 antibody can significantly improve the survival of mice implanted with CT26 cells [10]. In addition, stabilization of PD-L1 by CCL5 has been reported to inhibit the killing of the CRC cells by T cells and promote immune escape in vitro and in vivo [11].

Oncolytic vaccinia virus (OVV) is a type of immunotherapeutic that can eliminate cancer cells by directly killing cancer cells or indirectly inducing specific antitumor immunity [12]. Of interest, emerging evidence has indicated that the combination therapy of OVV with anti-PD-L1 antibody works synergistically to enhance the therapeutic efficacy in CC. Whereby, this combination reduces the exhaustion of PD-1-positive CD8+ T cells, enhances CD8+ T cell infiltration into the tumor, and strengthens their beneficial repertoire, reducing tumor burden and improving survival [13]. Furthermore, high CD8+ T cell infiltration into CC sensitizes CC to immune checkpoint blockade therapy, which can be used as a favorable tool to predict immunotherapy response and survival outcome [14].

Based on these lines of evidence, we presumed that the combined therapy of OVV and anti-PD-L1 antibody might suppress tumor cell growth and metastasis and promote antitumor immune responses. Herein, we attempted to explore the CD8+ T cell changes and CC growth and metastasis when utilizing OVV combined with the anti-PD-L1 antibody.

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