Tumor-infiltrating immune cells (TIICs) play essential roles in cancer development and progression. However, the association of TIICs with prognosis in colorectal cancer (CRC) patients remains elusive. Infiltration of TIICs was assessed using ssGSEA and CIBERSORT tools. The association of TIICs with prognosis was analyzed in 1,802 CRC data downloaded from the GEO (https://www.ncbi.nlm.nih.gov/geo/) and TCGA (https://portal.gdc.cancer.gov/) databases. Three populations of TIICs, including CD66b+ tumor-associated neutrophils (TANs), FoxP3+ Tregs, and CD163+ tumor-associated macrophages (TAMs) were selected for immunohistochemistry (IHC) validation analysis in 1,008 CRC biopsies, and their influence on clinical features and prognosis of CRC patients was analyzed. Prognostic models were constructed based on the training cohort (359 patients). The models were further tested and verified in testing (249 patients) and validation cohorts (400 patients). Based on ssGSEA and CIBERSORT analysis, the correlation between TIICs and CRC prognosis was inconsistent in different datasets. Moreover, the results with disease-free survival (DFS) and overall survival (OS) data in the same dataset also differed. The high abundance of TIICs found by ssGSEA or CIBERSORT tools can be used for prognostic evaluation effectively. IHC results showed that TANs, Tregs, TAMs were significantly correlated with prognosis in CRC patients and were independent prognostic factors (PDFS ≤ 0.001; POS ≤ 0.023). The prognostic predictive models were constructed based on the numbers of TANs, Tregs, TAMs (C-indexDFS&OS = 0.86; AICDFS = 448.43; AICOS = 184.30) and they were more reliable than traditional indicators for evaluating prognosis in CRC patients. Besides, TIICs may affect the response to chemotherapy. In conclusion, TIICs were correlated with clinical features and prognosis in patients with CRC and thus can be used as markers.

The polarization of tumor‐associated macrophages (TAMs) and tumor‐associated neutrophils (TANs), especially from the antitumoral phenotype to the protumoral phenotype under certain conditions, has an important influence on the progression of tumors. However, the interactions and combined prognosis of these cells are poorly known. Here, we detected the infiltration of CD68+ TAMs, CD163+ TAMs, and CD66b+ TANs in the specimens from 662 patients with GC by immunohistochemistry. The results showed that the infiltration of each of CD163+, CD68+, and CD66b+ cells in GC tissue was significantly increased and independently associated with GC prognosis. Strong collinearity (r = 0.690, P < 0.001) was found between the infiltration of CD163+ and CD68+ cells in GC, and multivariate Cox analysis confirmed the infiltration of CD163+ cells was a better predictor for prognosis than that of CD68+ cells. The combination of the infiltration of CD163+ and CD66b+ cells provided more accurate survival prediction than any individual marker. Patient subgroups with CD66blowCD163low (hazard ratio (HR) = 2.161; 95% confidence interval (CI)  = 1.266–3.688; P < 0.001), CD66bhighCD163high (HR = 3.575; 95% CI = 2.155–5.933; P < 0.001), and CD66blowCD163high (HR = 7.514; 95% CI = 4.583–12.312; P < 0.001) were gradually associated with shorter DFS when compared with the subgroup with CD66bhighCD163low. The similar result was also for DSS among the subgroups. Moreover, the two‐marker model could more effectively discriminate the prognosis among the patients with chemotherapy than that among those without chemotherapy. We concluded that CD163+ TAMs were a more valuable prognostic marker than CD68+ TAMs, and CD163+ TAMs combined with CD66b+ TANs could more precisely predict the prognosis of patients with GC.

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