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Myeloid‐derived suppressor cells (MDSCs) help establish the tumor microenvironment by suppressing T‐cell response in tumor‐bearing hosts. Plasmacytoid dendritic cells (pDCs) activate antigen‐specific T cells, thereby, maximizing their antitumor effects. IDO1 is associated with both MDSCs and pDCs and plays a major role in the formation of the tumor‐mediated immunosuppressive environment. We utilized immunohistochemistry to examine the involvement of IDO1 in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs, precancerous lesions). We examined the expression of MDSC markers, CD11b and CD33, as well as pDC markers, CD303 and IDO1, in 60 OSCC and 45 precancerous lesion specimens and analyzed their association with clinicopathological parameters. Expression of these biomarkers identifying MDSCs and pDCs was high in precancerous lesions in patients with severe dysplasia and OSCC. While detecting pDCs, high CD303 and IDO1 expression levels were frequently observed in moderately or poorly differentiated OSCCs. CD11b, CD33, and CD303 levels were significantly correlated with the mode of invasion; CD33 was correlated with OSCC invasion depth while the other three markers tended to be highly expressed in superficial cancer cases showing microinvasion. Expression levels of all four biomarkers were significantly associated with the cancerization of OPMDs to OSCCs. We show, for the first time, that the infiltration of MDSCs and pDCs is significantly associated with progression of premalignant lesions to OSCC. This suggests that these cells may act as prognostic biomarkers for premalignant lesion progression and that immunotherapeutic approaches that control each of these immunosuppressive cells may protect against progression to malignancy. [ABSTRACT FROM AUTHOR]

We retrospectively investigated the efficacy and toxicity of lapatinib plus capecitabine in 45 HER2-positive breast cancer patients. The median number of treatment courses was 6(1-22). Brain metastasis developed in 18 cases(40%), and 19 cases(42.2%)had received previous capecitabine treatment for metastatic breast cancer. The objective response rate(ORR=CR+PR)was 22.2%(10/45), and clinical benefit rate(CR+PR+long SD=24w)was 46.7%(21/45).The median time to progression(TTP)was 24.9 weeks(95% CI: 15.2 -34.6 ), and the median overall survival(OS)was 78.1 weeks(95% CI: 55.7 -100.5)in all 45 cases. The median TTP was significantly longer in patients who had not received capecitabine previously(30 vs 16 weeks, 95% CI: 16.3 -43.7, p=0.0051 ). There was no statistical difference in median OS associated with previous capecitabine exposure(42.7 weeks, 95% CI: 21.4 -64, p=0.057 ). The median TTP was significantly longer in patients who received less than 2 treatment regimens with trastuzumab for MBC rather than 3 regimens more(27.3 vs 16 weeks, p=0.0257 ), but there was no statistical difference in median OS(81 vs 40.9 weeks, p=0.26 ). Lapatinib in combination with capecitabine is likely more useful in patients who are naive to capecitabine, who received less than two regimens for metastatic breast cancer.