Anti-programmed cell death 1 (PD-1) and its ligand (PD-L1) has emerged as a novel immunotherapy for non-small cell lung cancer (NSCLC). However, the proportion of patients who may benefit from immunotherapy is limited and the factors sensitive or resistant to immunotherapy are not completely clear. Therefore, to identify reliable biomarkers as predictors of clinical response and resistance to anti-PD-1/PD-L1 therapies have become increasingly important. Here, we report a case of a patient with bone metastatic NSCLC, who achieved a pathologic complete response after preoperative pembrolizumab treatment. Postoperative pathological examination found no viable cancer cells in the resected pulmonary nodules and lymph nodes. Several high-frequency DNA damage response and repair (DDR) gene mutations including two germline mutations were identified in the primary lesion. Moreover, high PD-L1 expression, Kirsten rat sarcoma viral oncogene homolog (KRAS) combined with tumor protein 53 (TP53) mutations without epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) driver alterations, high infiltration level of CD8-positive cells and M1 macrophages were observed, which were favorable characteristics for immunotherapy. We explored the possible factors related to an excellent response to immune checkpoint inhibitor in this patient and determined that preoperative use of anti-PD-1 therapy might apply to late-stage lung adenocarcinoma patients with multidimensional advantageous biomarkers for treatment with immune checkpoint inhibitors (ICIs). Key points• We characterized the genomic features and immune microenvironment signature of a lung adenocarcinoma in a patient with bone metastasis who achieved pathologic complete response after pembrolizumab treatment. • To evaluate multidimensional advantageous biomarkers for immunotherapy. Figure 2 Tumor immune microenvironment signature of the patient's pulmonary lesion on needle biopsy. (a) Images show five-color mIHC (PD-L1, CD8, CD68, CD163, DAPI) in the primary lesion. Nuclei were counterstained with DAPI. Magnification, ×200. (b) Quantitative mIHC results of PD-L1, CD8, CD68, ( ) Stroma region, ( ) Tumor region. (c) The proportion of CD68 + CD163 − cells ( ) and CD68 + CD163 + cells ( ) in CD68 + cells from six random vision fields.
Background Mean platelet volume (MPV) is a marker of platelet activation, which is usually negatively correlated with platelet count (PC). The ratio of MPV to PC (MPV/PC) has an essential role in the diagnosis of multiple malignancies. However, only a few studies investigated the value of MPV/PC in colorectal cancer (CRC) and the combination of MPV/PC with tumor markers in CRC. This retrospective clinical study aimed to evaluate the diagnostic value of MPV/PC and tumor markers (CA72-4, CA125, CA199) used alone or in combination in CRC. Methods 200 patients with CRC and 317 patients with colorectal benign polypus pathologically diagnosed during 2019/01/04 to 2022/06/30 were included. Hematological and pathological parameters of the above patients were collected, data were analyzed with Student’s t-test, one-way ANOVA or Kruskal-Wallis H test and receiver operating characteristic (ROC) curve, and ROC curve was used to evaluate the diagnostic value of tumor markers and MPV/PC used alone or in combination in CRC. Results The MPV/PC in CRC group was significantly lower than the control group (P < 0.0001). Among the three tumor markers, higher CA125 was correlated with distant metastasis and lower differentiation (P < 0.05), increased CA72-4 indicated positive nerve invasion (P = 0.0174), and elevated CA199 was associated with lymphatic metastasis and positive vascular invasion (P < 0.05). For subgroups regarding tumor anatomical location, both CA125 and CA199 were higher in colon cancer group than rectum cancer group (P = 0.0322, P = 0.0094). MPV/PC was associated with tumor infiltration, regional lymph node metastasis, differentiation and nerve invasion (P < 0.05) and the combination of MPV/PC with the three tumor markers produced a larger AUC with higher sensitivity, specificity and Yuden index than MPV/PC or the three tumor markers used alone to distinguish between CRC and colorectal polyps. Conclusion Preoperative MPV/PC in peripheral blood of patients with CRC was lower than the control group. Meanwhile, the combined detection of tumor markers with MPV/PC can improve the diagnostic value of CRC, revealing the potential of MPV/PC as a promising screening tool in CRC early diagnosis.
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