The Immune System & Tumor Microenvironment – A New Tool for Survival in Colorectal Cancer

Stage III colorectal cancer is a stage in which cancer has spread beyond the bowel wall into surrounding tissues and metastasized to at least one, but usually more, regional lymph node. At this stage, the cancer has not yet spread to distant organs (such as the liver or lungs).

In the treatment of stage III colorectal cancer, surgery is the first step to remove the affected tumor and lymph nodes. This may be followed by adjuvant chemotherapy to prevent cancer recurrence (its return). Radiotherapy may be used before or after surgery to shrink or destroy the tumor, particularly in the treatment of rectal cancer.

Although patients may share the same diagnosis of stage 3 colorectal cancer, we know that some tumors have more aggressive biological characteristics and tend to recur, whereas others respond better to treatment. Identifying tumors that may behave differently despite being at the same stage is therefore a critical issue in oncology when planning treatment.

Predicting the Course of Stage 3 Colorectal Cancer with the Immunoscore Test

Colorectal cancer, which affects millions of people worldwide, remains a serious health problem. Early diagnosis and effective treatments are vital to managing this disease. In recent years, scientists seeking to better understand its course and improve treatment outcomes have focused on the complex interaction between tumor biology and the immune system. At the center of these efforts is Immunoscore, which has emerged as an important prognostic factor, particularly in the treatment of stage III colorectal cancer.

Immunoscore is a biomarker used to predict recurrence risk in early-stage colorectal cancer. This method focuses on the center and surrounding margins of tumor tissue, where CD3-positive and CD8-positive T-cell responses are measured. It therefore allows Immunoscore to evaluate the tumor microenvironment by measuring the status of immune cells and assessing the interaction between the tumor and the immune system. This interaction plays a decisive role in tumor growth, spread, and response to treatment.

Research Findings

A study aimed at determining the value of Immunoscore was published on 14 March 2024 in the Journal of Clinical Oncology. It involved patients with stage III colorectal cancer treated with adjuvant mFOLFOX6 or CAPOX chemotherapy regimens. The study showed that Immunoscore could significantly predict patients' disease-free survival. In particular, patients with Immunoscore-Low had significantly shorter disease-free survival than those with Immunoscore-High.

Results

1. Immunoscore Assessment: In the study, Immunoscore was determined in 99.5% of the 2,608 patients with suitable samples. Of these patients, 877 (33.7%) were classified as Immunoscore-Low and 1,731 as Immunoscore-High.
2. Treatment Distribution: A total of 834 patients (32%) received mFOLFOX6, while 1,774 (68%) received CAPOX.
3. Risk Status and Age Group: Immunoscore-Low tumors were more common in higher-risk patients (T4 or N2; 52.9%) and younger patients (compared with 42.2%, P < 0.001) (P = 0.024).
4. Disease-Free Survival Rates:
   • In the mFOLFOX group, the 3-year disease-free survival rate was 65.1% for Immunoscore-Low patients and 79.4% for Immunoscore-High patients.
   • In the CAPOX group, these rates were 69.8% and 79.4%, respectively.
   • When both groups were combined, the rate was 68.6% for Immunoscore-Low patients and 79.4% for Immunoscore-High patients.
5. Multivariate Analysis Results: In multivariate analysis, patients with Immunoscore-Low tumors had significantly shorter disease-free survival than those with Immunoscore-High tumors. This held true regardless of sex, body mass index, clinical risk group, tumor location, treatment duration, or chemotherapy regimen.
   • In the CAPOX group, HR = 1.52 (95% CI = 1.28–1.82),
   • In the mFOLFOX6 group, HR = 1.58 (95% CI = 1.22–2.04),
   • In the combined groups, HR = 1.55 (95% CI = 1.34–1.79).
6. Prognostic Value by Age and MMR Status:
   • In the CAPOX group, Immunoscore was a stronger prognostic factor in patients younger than 65 (HR = 1.92, P < 0.001) than in patients older than 65 (HR = 1.28, P = 0.043; P for interaction = 0.026).
   • Immunoscore was a strong prognostic factor among patients with proficient DNA mismatch repair (MMR) (HR = 1.68, P < 0.001), but had no prognostic value among MMR-deficient patients (HR = 0.67, P = 0.57; P for interaction = 0.03).

What Does This Study Mean for Clinical Practice?

These findings indicate that Immunoscore is an important tool for predicting disease-free survival in patients with stage III colorectal cancer. Patients with Immunoscore-Low may need closer follow-up or additional treatments, and Immunoscore analysis may be an influential factor in determining treatment duration and intensity.

Interaction Between the Tumor Microenvironment and the Immune System

Immunoscore analysis provides a comprehensive assessment of the tumor microenvironment. By helping us understand the interaction between the tumor and the immune system, this analysis provides important information about how the tumor "looks" to the immune system and how the immune system responds to it. The tumor's aggressiveness and biological characteristics shape this interaction. Immunoscore therefore functions as a complex marker reflecting both tumor biology and the immune system's response.

Conclusion

Immunoscore is an important tool in the treatment of stage III colorectal cancer for predicting patients' prognosis and response to treatment. By enabling the development of personalized treatment approaches, this analysis helps identify more effective treatment strategies for patients. However, further research and validation studies are needed to reveal its full potential and achieve wider acceptance in clinical practice. This approach may offer new hope in colorectal cancer treatment and represents an important step in the fight against cancer.