Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

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6.4. Phenotypic and Functional Characteristics of Immune Cells Present at the Tumor Site Tab. 6.1 Morphologic, phenotypic and functional characteristics of TIL found in human solid tumors 1. Morphology small to large lymphocytes 2. Phenotype CD3 + TCRa/b + T cells; few (
102 6 Immune Cells in the Tumor Microenvironment which enable them to survey the target for the presence of class I MHC molecules [40]. These receptors are of two types: killer inhibitory receptors (KIRs) and killer activating receptors (KARs) [41, 42]. NK cell functions and their interactions with other cells or the extracellular matrix (ECM) molecules are regulated through these receptors and Fcg receptors (FcgRs). NK cells are strategically distributed throughout body fluids and tissues. Studies of NK cell localization in human tissues have been difficult, however, because immunostaining for NK cells has not been reliable. The anti-NK cell antibodies which work well in flow cytometry are not useful for phenotyping in tissues, especially in paraffin-embedded human specimens [43]. Antibodies specific for perforin or granzymes are more reliable immunostaining reagents, with a caveat that activated cells other than NK cells may be enriched in granules containing these components. Therefore, much of the information about NK cell distribution in human tissues, including tumors, is derived from studies performed with freshly isolated NK cells using flow cytometry for phenotyping and 51 Cr-release assays with K562 as targets, which measure the capability of these effector cells to induce secretory or necrotic killing [37]. Tissues that are known to contain the largest proportions of activated NK cells include the liver, lungs and the placenta during pregnancy [36, 43]. Lymphocytic infiltrates associated with infections in these organs contain numerous activated NK cells [44]. Importantly, however, hepatocellular carcinomas, colon tumors metastatic to liver, lung cancers or ovarian carcinomas are not found to be enriched in NK cells [43]. In general, few NK cells have been observed in lymphocytic infiltrates of human solid tumors and particularly of advanced lesions, although they may be a more prominent component of early lesions or tumors associated with viral infections, such as the cervical carcinoma [18, 36]. The presence of NK cells in inflammatory but not neoplastic conditions suggests either that their primary biologic role is elimination of infectious targets rather than tumor cells [45] or that the tumor microenvironment preferentially induces their demise. The available evidence appears to point to the latter possibility. Indeed, it has been observed that NK cells purified from ascites of women with ovarian carcinoma have profoundly depressed responses to IL-2 (Fig. 6.4) [46] and express low levels of message for IFN-_ but significantly increased levels of mRNA for IL-10 compared to normal circulating NK cells (Fig. 6.5). Furthermore, relative to normal NK cells, decreased or absent expression of the z chain, associated in NK cells with FcgRIII, was observed in NK cells obtained from ovarian ascites as well as in circulating NK cells of patients with several types of cancer, including melanoma (Fig. 6.6). Our recent studies suggest that among circulating NK cells in patients with breast cancer, a subset of CD56 bright CD16 dim NK cells, which represents about 95% of all NK cells and is responsible for effector functions, preferentially binds Annexin V and thus is primed for apoptosis (unpublished data). These patients also had significantly lower NK activity than the age- and sex-matched healthy controls tested in parallel, an indication that Annexin-binding NK cells were indeed functionally impaired. These and other recent observations suggest that endogenous circulating or tissue-resident NK cells have the potential to play a role in tumor surveillance and control of metastasis dissemination. However, once the tumor is established, it might subvert anti-tumor functions of NK cells, especially in
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Cancer Immune Therapie: Current and
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Editors: Dr. Gernot Stuhler Univers
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VI Preface Recent years have seen a
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VIII Contents 2.5.3 Antigens Encode
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X Contents 6.4.2 Natural Killer (NK
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XII Contents 9.6 Loading DC with An
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XIV Contents 14.2.2.1 Cancer-specif
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List of Contributors Richard Bucala
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Color Plates Fig. 5.2 The MHC class
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Fig. 5.5 Different immune effector
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Fig. 5.17 Possible pathway for the
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Fig. 6.2 T lymphocytes in the tumor
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Index a acidic and basic fibroblast
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±, see also tumors cationic lipids
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e EBV see Epstein-Barr virus EDR se
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immature Mo-DCs 184 immune cells ±
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MHC class I antigen-processing mach
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±, onco- 209 ±, over-expressed ce
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TICD see tumor-induced cell death T
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Part 1 Tumor Antigenicity Cancer Im
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4 1 Search for Universal Tumor-Asso
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10 1 Search for Universal Tumor-Ass
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18 2 Serological Determinants On Tu
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30 Cancer Immune Therapie: Current
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32 3 Processing and Presentation of
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42 4 T Cells In Tumor Immunity cult
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44 4 T Cells In Tumor Immunity cell
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46 4 T Cells In Tumor Immunity to T
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Page 157 and 158: 122 7 Immunosuppresive Factors in C
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152 7 Immunosuppresive Factors in C
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154 7 Immunosuppresive Factors in C
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156 8 Interleukin-10 in Cancer Immu
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Part 3 Strategies for Cancer Immuno
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180 9 Dendritic Cells and Cancer: P
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206 10 The Immune System in Cancer:
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232 11 Hybrid Cell Vaccination for
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254 12 Principles and Strategies Em
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270 13 Applications of CpG Motifs f
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288 14 The T-Body Approach: Towards
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300 15 Bone Marrow Transplantation
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312 16 Immunocytokines: Versatile M
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348 17 Immunotoxins and Recombinant
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382 Glossary tion to the variable d
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384 Glossary suppressor gene produc
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386 Glossary press the proper recep
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388 Glossary gp96 See Chaperone. Gr
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390 Glossary cytes and addressing l
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392 Glossary T bodies are being tes
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