This study attempts to employ a combination therapy using rhG-CSF, IL-2, and PD-1 inhibitors, aiming to overcome the limitations of monotherapy in immunotherapy through multi-faceted immune regulation. By modulating the immune microenvironment to enhance immune cell infiltration, and breaking through the physical and immunosuppressive barriers of tumors, it seeks to augment the efficacy of immunotherapy. This approach explores the effectiveness of a neoadjuvant treatment model in cases of liver metastasis.

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.

Inclusion Criteria:

1. Age ≥18 years and ≤75 years
2. Histologically confirmed colorectal adenocarcinoma
3. pMMR (proficient mismatch repair) or MSI-L (microsatellite instability-low) or MSS (microsatellite stable)
4. Synchronous liver metastases
5. Achievable NED (No Evidence of Disease) status
6. CRS (Clinical Risk Score) of 3-4 points
7. ECOG (Eastern Cooperative Oncology Group) Performance Status score ≤ 1

Exclusion Criteria:

1. Recurrent colorectal cancer with active bleeding, perforation, or complex conditions requiring urgent surgery; or concurrent non-colorectal cancer malignancies.
2. Patients who have previously received systemic anticancer therapy for colorectal cancer; or have been treated with PD-1, PD-L1, or CTLA-4 antibodies.
3. Patients with any active autoimmune disease; known or tested positive for Human Immunodeficiency Virus (HIV) or Acquired Immunodeficiency Syndrome (AIDS); or a history requiring steroid or immunosuppressive drug treatment.
4. Patients with interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (such as diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
5. Patients who experienced any Grade 2 or higher toxicities due to prior treatments (as classified by the Common Terminology Criteria for Adverse Events [CTCAE] version 5), which have not resolved (excluding anemia, alopecia, and skin pigmentation changes); known or suspected history of hypersensitivity to any of the drugs used in the trial.
6. Pregnant or breastfeeding women.

1. Age ≥18 years and ≤75 years
2. Histologically confirmed colorectal adenocarcinoma
3. pMMR (proficient mismatch repair) or MSI-L (microsatellite instability-low) or MSS (microsatellite stable)
4. Synchronous liver metastases
5. Achievable NED (No Evidence of Disease) status
6. CRS (Clinical Risk Score) of 3-4 points
7. ECOG (Eastern Cooperative Oncology Group) Performance Status score ≤ 1