Colorectal cancer stands as a prominent global health issue, ranking among the most
prevalent malignancies worldwide. Its incidence exhibits distinct geographical
variations, with higher rates observed in developed countries. Age is a significant risk
factor, primarily affecting individuals aged 50 and above, although a concerning trend of
increasing incidence in younger adults has emerged in recent years. There exists a gender
disparity, with a slightly higher prevalence in males. Notably, lifestyle factors,
including dietary choices, sedentary habits, smoking, and obesity, play pivotal roles in
its pathogenesis. These epidemiological patterns underscore the urgency of implementing
effective prevention strategies and advancing early detection methods to mitigate the
impact of the disease.
The poor prognosis in colorectal cancer patients primarily stems from the tumor's
aggressive biological properties and its propensity for distant metastasis. The unique
anatomy of the liver, endowed with both the portal venous and hepatic arterial systems,
and abundant blood supply, renders it the most common site for distant metastasis from
colorectal cancer. Currently, radical surgical resection remains the primary treatment
for colorectal liver metastases; however, due to tumor burden and clinical complications,
only 17% to 20% of patients with colorectal liver metastases are amenable to surgery.
With advancements in therapeutic modalities and the precision of medical approaches, a
comprehensive treatment paradigm combining surgery, radiofrequency ablation,
postoperative targeted drugs, and interventional therapies has gradually taken shape.
Although this has enriched treatment options for colorectal liver metastases and improved
outcomes, many patients present with multifocal intrahepatic metastases and severe
complications at diagnosis, precluding further surgical intervention and resulting in
limited survival and poor prognosis. In recent years, immunotherapy for tumors has
garnered unprecedented attention and extensive clinical application, fundamentally
relying on enhancing the patient's own immune capabilities to bolster antitumor activity.
The ongoing in-depth investigation into the programmed cell death receptor 1
(PD1)/programmed cell death ligand 1 (PDL1) signaling pathway has also presented new
opportunities for patients with colorectal liver metastases.
In colorectal cancer, the PD-1 inhibitory pathway plays a central role in regulating
immune cell exhaustion. However, a majority of colorectal cancer patients exhibit limited
response to monotherapy targeting PD-1, suggesting that combinations of PD1 inhibitors
with other immunostimulatory agents may address this challenge. Some of these combination
therapies have made progress in animal models and are being tested in clinical studies.
Among them, interleukin-2 (IL-2) emerges as a promising candidate to synergize with PD-1
blockade in exerting antitumor effects. Meanwhile, recombinant human granulocyte
colony-stimulating factor (rhG-CSF) has been primarily utilized in oncology for two
purposes: first, to prevent and treat neutropenia induced by chemotherapy or
radiotherapy; second, as a priming strategy to augment the efficacy of chemotherapy. Our
study aims to explore a combination therapy employing rhG-CSF, IL-2, and PD-1 inhibitors,
with the objective of overcoming the limitations of single-agent immunotherapy through
multifaceted immune modulation. By modulating the immune microenvironment to enhance
immune cell infiltration and breach the physical and immunosuppressive barriers of
tumors, we seek to potentiate the effects of immunotherapy and investigate the efficacy
of a neoadjuvant treatment model in liver metastases.