Intratumoral infiltrating lymphocytes correlate with improved survival in colorectal cancer patients: Independent of oncogenetic features.
BACKGROUND
The clinical relevance and prognostic value of tumor-infiltrating lymphocytes (TILs) as an interplay between malignant cells and immune function has been known for decades. On contrary, this potential may be different by T lymphocytes subsets endowed with a different function. Colorectal cancer (CRC) is a heterogeneous disease with different suggested prognostic biomarkers. So, this study was conducted to examine the prognostic value of CD8+ TILs on the survival rate of CRC as an independent factor of oncogenetic tumor features.


METHODS
With respect to this, 281 formalin-fixed, paraffin-embedded tissue samples of Iranian CRC patients were evaluated for clinical features including tumor location, tumor stage, differentiation grade, and mucinous characteristics. Then, using the standard immunohistochemical technique, tumor sections were examined, and CD8+ TILs were counted and identified in two regions of the tumor, including intratumoral (ITCIL TILs) and stromal (S TILs). The prognostic value of CD8+ TILs was determined by comparing with parameters, such as diagnostic age, tumor stage, adjuvant therapy, microsatellite instability (MSI) status, KRAS and BRAF mutations, family history, and survival.


RESULTS
The presence of intratumoral tumor cell-infiltrating lymphocytes (ITCIL) CD8+ lymphocytes are significantly associated with differentiation (p = 0.004), tumor, node, and metastases (TNM) stage (p = 0.001), and MSI (p = 0.001). Meanwhile, based on the level of stromal infiltrating lymphocytes (SIL) infiltration, analysis of CRC patients was statistically associated with a location (p = 0.002), TNM stage (p < 0.001), metastasis (p < 0.001), and KRAS mutation (p = 0.031). Also, tumors with severe ITCIL CD8+ lymphocytes have a good prognosis compared with tumors with poor or moderate ITCIL CD8+ lymphocytes.


CONCLUSIONS
These results suggest that intratumor cell-infiltrating CD8- T lymphocytes as an independent prognostic factor that have an antitumor activity as judged by their favorable effect on patients' survival and could potentially be exploited in the treatment of CRC.
['Nazemalhosseini-Mojarad|Ehsan|E|0000-0001-8914-004X', 'Mohammadpour|Somayeh|S|', 'Torshizi Esafahani|Amir|A|', 'Gharib|Ehsan|E|', 'Larki|Pegah|P|', 'Moradi|Afshin|A|', 'Amin Porhoseingholi|Mohammad|M|', 'Asadzade Aghdaei|Hamid|H|', 'Kuppen|Peter J K|PJK|', 'Zali|Mohammad Reza|MR|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D018414:CD8-Positive T-Lymphocytes D002454:Cell Differentiation D015179:Colorectal Neoplasms D005260:Female D006801:Humans D008207:Lymphatic Metastasis D016246:Lymphocytes, Tumor-Infiltrating D008297:Male D053842:Microsatellite Instability D008875:Middle Aged D009154:Mutation D009367:Neoplasm Staging D048493:Proto-Oncogene Proteins B-raf D016283:Proto-Oncogene Proteins p21(ras) D013997:Time Factors
colorectal cancer tumor-infiltrating lymphocytes prognostic biomarker