三田 恭義

Tumor-specific CD8+ T cells play a pivotal role in anti-tumor immunity and are a key target of immunotherapeutic approaches. Intratumoral CD8+ T cells are heterogeneous; Tcf1+ stem-like CD8+ T cells give rise to their cytotoxic progeny - Tim-3+ terminally differentiated CD8+ T cells. However, where and how this differentiation process occurs has not been elucidated. We herein show that terminally differentiated CD8+ T cells can be generated within tumor-draining lymph nodes (TDLNs) and that CD69 expression on tumor-specific CD8+ T cells controls its differentiation process through regulating the expression of the transcription factor TOX. In TDLNs, CD69 deficiency diminished TOX expression in tumor-specific CD8+ T cells, and consequently promoted generation of functional terminally differentiated CD8+ T cells. Anti-CD69 administration promoted the generation of terminally differentiated CD8+ T cells, and the combined use of anti-CD69 and anti-PD-1 showed an efficient anti-tumor effect. Thus, CD69 is an attractive target for cancer immunotherapy that synergizes with immune checkpoint blockade.

Preoperative simulation using a three-dimensional printer is effective to perform safe surgery by knowing the range limit of drilling in the temporal bone. Moreover, simulations using models are thought to be useful for education of young surgeon.

内視鏡下に鼻副鼻腔腫瘍を切除するにあたって,重要な点の一つにワーキングスペースの確保と明視下に腫瘍基部を同定することが挙げられる。鼻中隔の開窓による両側鼻腔アプローチは非常に有用な方法であり,大きなワーキングスペースを得ることができるが,術後に大きな鼻中隔穿孔を生じるリスクがある。今回,頭側後方茎の鼻中隔粘膜弁挙上による鼻中隔の開窓により,内視鏡下に切除可能であった鼻腔粘膜悪性黒色腫を経験した。症例は70歳代の男性であり,右下鼻甲介から発生したと考えられる悪性黒色腫が前鼻孔から上咽頭まで充満していた。手術は全過程を内視鏡下に行った。頭側後方茎の鼻中隔粘膜弁挙上による鼻中隔開窓とmedial maxillectomyを行うことで,内視鏡と手術器具を操作でき,更には腫瘍を外側に移動させ得るワーキングスペースを確保した。これにより,腫瘍基部を下鼻甲介の後方内側粘膜と同定し,下鼻甲介ごと一塊切除を行うことができた。鼻中隔の開窓時に患側鼻中隔粘膜は切除したが,鼻中隔粘膜弁の切開ラインを工夫したことで術後の鼻中隔穿孔は軽微にとどめられた。頭側後方茎の鼻中隔粘膜弁挙上による鼻中隔開窓は鼻腔悪性腫瘍の切除において有効な手法と考えられた。(著者抄録)

This report is the first to document TEN caused by nivolumab treatment in head and neck cancer. We believe this article can contribute significantly in understanding the principles of nivolumab treatment in patients with head and neck cancer.

Background: Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. Methods: This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multi-center study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders.The levels of JC pollen-specific IL-10(+)Foxp3(+) cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. Results: The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10(+)Foxp3(+) cells increased only in these good responders. Conclusions: Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10(+)Foxp3(+) cells could be objective biomarkers for SLIT.

症例は71歳，男性．Vogt-小柳-原田病の精査加療中，全身CTで食道壁肥厚を指摘され，当科紹介となった．上部消化管内視鏡検査でMtに2型腫瘤を認め，組織診の結果内分泌細胞癌の診断であった．PETおよびCTでは主病巣の他，3領域にわたり多数の転移リンパ節を認めた．遠隔転移は認めず，cT3 N2 M0 stage IIIと診断した．術前補助化学療法（NAC）としてCPT-11+CDDP投与を2コース施行し，腫瘍は著明に縮小．PRの判定となった．右開胸開腹食道切除+胃管再建+3領域リンパ節郭清術を施行し，NACの組織学的効果判定はGrade 2，郭清リンパ節123個にviableな腫瘍細胞を認めなかった．術後CPT-11+CDDPを1コース追加し，現在まで再発なく経過している．食道内分泌細胞癌は稀な疾患で治療法も確立されていないが，NACと手術による集学的治療が有効である可能性が示唆された．