Density and location of CD3⁺ and CD8⁺ tumor‐infiltrating lymphocytes correlate with prognosis of oral squamous cell carcinoma

Abstract

Background Tumor‐infiltrating lymphocytes (TILs) are regarded as adaptive immune response of the host to cancer cells and valuable prognostic factors. Here, we sought to characterize the densities and locations of CD3+ and CD8+ TILs in primary oral squamous cell carcinoma (OSCC) samples and assess their clinicopathological and prognostic significance. Methods A total number of 169 OSCC samples from 2 independent patient cohorts (Nanjing cohort, 93 cases; Wuxi cohort, 76 cases) were retrospectively collected. The numbers of CD3+ and CD8+ TILs at tumor center (CT) and invasive margin (IM) of OSCC were identified by immunohistochemistry and calculated. The optimal cutoff values for CD3+ and CD8+ TILs to stratify patients were determined by X‐tile software in Nanjing cohort and further utilized in Wuxi cohort. The associations between CD3+/CD8+ TILs and clinicopathological parameters or patient survival were assessed. The prognostic values of CD3+/ CD8+ TILs were evaluated by Cox regression analyses. Results CD3+ and CD8+ TILs were identified at both CT and IM and enriched at IM. High density of CD3+ TILs at IM (CD3 IM) was significantly associated with increased overall and disease‐specific survival (P < .05). High density of CD8+ TILs at CT (CD8 CT) was significantly associated with increased overall but not disease‐specific survival. Moreover, CD3 IM and CD8 CT were identified as independent prognostic factors for patient survival. Conclusions Our findings provide further evidence to support the prognostic values of CD3+ and CD8+ TILs for OSCC, suggesting that TIL subsets might be viable biomarkers and therapeutic targets with translational significance.

Preoperative circulating platelet, neutrophil, and lymphocyte counts predict survival in oral cancer

“…Mounting evidence has established that deregulated immune of host and excessive systemic or local inflammation facilitates tumor overgrowth, metastatic spreading, and therapeutic resistance (Diakos, Charles, McMillan, & Clarke, ; Shalapour & Karin, ). Previous reports have revealed that the presence and functional status of tumor‐infiltrating lymphocytes usually significantly associate with tumor onset and progression as well as clinical response to immunotherapy (Bindea, Mlecnik, Angell, & Galon, ; Zhou et al, ). Measurements of tumor‐infiltrating neutrophils, lymphocytes, and macrophages have indicated their prognostic values in a broad spectrum of human cancers (Galon et al, ; Nguyen et al, ).…”

Development and validation of a seven‐immune‐feature‐based prognostic score for oral squamous cell carcinoma after curative resection

“…For example, intratumoral infiltration by diverse types of lymphocytes (tumor‐infiltrating lymphocytes, TILs) has been associated with favorable or inferior prognoses in several human cancers including OSCC . We have recently reported that high densities of CD3 + and CD8 + TILs at tumor invasive margins (IM) as well as CD45RO + at tumor center (CT) in OSCC were significantly associated with increased overall and disease‐specific survival and served as independent prognostic factors for patient survival . However, given the complex immune contexture in human tumors, assessment of individual types of TIIs might have prognostic prediction with moderate accuracy .…”

“…6,7,[10][11][12][13] We have recently reported that high densities of CD3 + and CD8 + TILs at tumor invasive margins (IM) as well as CD45RO + at tumor center (CT) in OSCC were significantly associated with increased overall and disease-specific survival and served as independent prognostic factors for patient survival. 14,15 However, given the complex immune contexture in human tumors, assessment of individual types of TIIs might have prognostic prediction with moderate accuracy. 16 Integrating multiple immune features into a single model would substantially improve the prognostic value and power over that of single biomarker.…”

Disruption of sialic acid metabolism drives tumor growth by augmenting CD8+ T cell apoptosis

“…The increased tumor growth of MC38‐Sia null cells could be attributed to reduced CD8 + T cell frequencies present within the tumor. Reduced migration of CD8 + T cells toward the tumor core has been correlated with bad prognosis . As we did not address the localization of the T cells within the tumor microenvironment, we cannot rule out that CD8 + T cells were hampered in reaching the tumor core.…”