# Increased Infiltration of CD4 +, CD8 +, and CD68 + Cells at the Invasive Front Is Associated With Favorable Prognosis in Obstructive Colorectal Cancer: A Retrospective Observational Study

**Authors:** Goro Takahashi, Seiichi Shinji, Toshiyuki Ishiwata, Takeshi Yamada, Kay Uehara, Akihisa Matsuda, Tomio Arai, Ryuji Ohashi, Yasuyuki Yokoyama, Takuma Iwai, Hiroshi Yoshida

PMC · DOI: 10.1002/cnr2.70508 · 2026-03-06

## TL;DR

High levels of CD4+, CD8+, and CD68+ immune cells at the tumor edge in obstructive colorectal cancer are linked to better survival outcomes.

## Contribution

This study identifies immune cell infiltration at the tumor invasive front as a strong independent prognostic factor in obstructive colorectal cancer.

## Key findings

- CD4+, CD8+, and CD68+ cells are more abundant at the tumor invasive front than in the tumor center.
- High CD4+ and CD68+ cell densities at the invasive front correlate with improved cancer-specific survival.
- Total immune cell density at the invasive front is the strongest independent predictor of survival.

## Abstract

Obstructive colorectal cancer (OCRC) presents as an oncologic emergency with poor prognosis. Although tumor‐infiltrating lymphocytes (TILs) and tumor‐associated macrophages (TAMs) are known to affect colorectal cancer outcomes, their roles in OCRC remain unclear.

We retrospectively analyzed 66 patients with Stages II–III OCRC who underwent curative resection following endoscopic decompression. CD4+, CD8+, and CD68+ cell densities at the tumor center and invasive front were quantified using multiplex immunofluorescence imaging. Cancer‐specific survival (CSS) was assessed in relation to immune cell infiltration. Target immune cells were significantly more abundant at the invasive front compared to the tumor center. High densities of CD4+ TILs and CD68+ TAMs at the invasive front were associated with superior CSS (p = 0.0079 and p = 0.0088, respectively). Total immune cell density—defined as the sum of CD4+, CD8+, and CD68+ cells/mm2—was the strongest independent prognostic factor (HR = 30.8, p < 0.001).

High immune cell infiltration at the invasive front was associated with favorable prognosis, even in OCRC. As the invasive front represents the interface between host and tumor, assessment of the tumor immune microenvironment at this site may refine risk stratification and optimize clinical management in OCRC patients.

## Linked entities

- **Proteins:** CD4 (CD4 molecule), CD8A (CD8 subunit alpha), CD68 (CD68 molecule)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}
- **Diseases:** death (MESH:D003643), PNI (MESH:D044342), Obstructive Colorectal Cancer (MESH:D015179), II (MESH:C537730), Stages II-III (MESH:D062706), oncologic (MESH:D000072716), dilation of the colon (MESH:D003108), TICD (MESH:D002292), TDT (MESH:D003665), bacterial (MESH:D001424), tumor node metastasis (MESH:D008207), abdominal distension (MESH:D000007), perforation (MESH:D057112), II-III (MESH:C536044), CAFs (MESH:D009369), electrolyte (MESH:D014883), Bowel obstruction (MESH:D012778), inflammation (MESH:D007249), SEMS (MESH:D013651), pap (MESH:C535787), stenosis (MESH:D003251), specific (MESH:D000080888), TAM (MESH:D020914)
- **Chemicals:** Opal (-), formalin (MESH:D005557), 4',6-diamidino-2-phenylindole (MESH:C007293), paraffin (MESH:D010232)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** OCRC — Homo sapiens (Human), Colorectal carcinoma, Cancer cell line (CVCL_A1EX)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12965902/full.md

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Source: https://tomesphere.com/paper/PMC12965902